The Human Obesity Gene Map: The 2005 Update

Authors


Human Genomics Laboratory, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808-4124. E-mail: Bouchac@PBRC.edu

Abstract

This paper presents the 12th update of the human obesity gene map, which incorporates published results up to the end of October 2005. Evidence from single-gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, transgenic and knockout murine models relevant to obesity, quantitative trait loci (QTL) from animal cross-breeding experiments, association studies with candidate genes, and linkages from genome scans is reviewed. As of October 2005, 176 human obesity cases due to single-gene mutations in 11 different genes have been reported, 50 loci related to Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and causal genes or strong candidates have been identified for most of these syndromes. There are 244 genes that, when mutated or expressed as transgenes in the mouse, result in phenotypes that affect body weight and adiposity. The number of QTLs reported from animal models currently reaches 408. The number of human obesity QTLs derived from genome scans continues to grow, and we now have 253 QTLs for obesity-related phenotypes from 61 genome-wide scans. A total of 52 genomic regions harbor QTLs supported by two or more studies. The number of studies reporting associations between DNA sequence variation in specific genes and obesity phenotypes has also increased considerably, with 426 findings of positive associations with 127 candidate genes. A promising observation is that 22 genes are each supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. The electronic version of the map with links to useful publications and relevant sites can be found at http:obesitygene.pbrc.edu

Introduction

This paper represents the 12th in a series (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11) on the status of the human obesity gene map, the 11th report published in Obesity. As in previous reports, we reviewed the literature published up to the end of October 2005 searching for the relevant publications through a variety of sources: PubMed using a combination of key words, authors, and journals; continuous reviews of obesity and genetics journals; personal collection of reprints; and papers made available to us by colleagues from around the world. Publications dealing with a wide variety of phenotypes pertaining to obesity, such as BMI, body fat mass, percentage of body fat, abdominal fat, fat-free mass, skinfolds, resting metabolic rates, plasma leptin levels, and other components of fat distribution and energy balance, were retained. As in previous reports, negative findings are not systematically reviewed but are briefly introduced when such data were available to us.

Each collaborating author was assigned one section of the report for an in-depth review. In addition to an introduction and a brief discussion (C.B), the report includes sections dealing with monogenic obesity cases (G.A.), Mendelian disorders exhibiting obesity as clinical feature (J.W.), murine gene-deficient [knockout (KO)1/floxed], transgenic models in which altered expression of a gene (or genes) results in phenotypes relevant to obesity and quantitative trait loci (QTL) from murine models (A.Z.), QTLs from other animal model studies and gene-drug interactions (Y.C.), association studies in humans with specific candidate genes (T.R.), and human linkage studies including genome scans performed to identify QTLs of obesity or obesity-related phenotypes (L.P.). The other collaborating author (B.W.) is involved in the management of the database, the generation of the tables and the map from the database, and the electronic version of the human obesity gene map (http:obesitygene.pbrc.edu). Readers are referred to previous publications (9, 11) for detailed information on the electronic version of the map and on browsing and querying capabilities of the online Obesity Gene Map Database.

As in the past, the published references for each entry in the current human obesity gene map are provided for convenience. We are using gene symbols and chromosomal locations given in the Entrez Gene database (http:www.ncbi.nlm.nih.gov) available from the National Center for Biotechnology Information. The appendix provides a complete list of genes and map locations cited in this paper.

Although the authors have taken every possible effort to provide correct information, in the rapidly changing world of genetics and bioinformatics and the ever-present world of human fallibility, it is almost inevitable that inaccuracies will emerge. The full responsibility for errors is ours. Furthermore, we seek your indulgence in errors of omission and hope you will notify us of any oversights. All correspondence to maximize the precision and quality of the map is welcomed and, indeed, solicited.

Sadly, we have to inform the readership that this is likely to be the last time that we are able to publish the review of the human obesity gene map. We have tried unsuccessfully to obtain the funding to support the enormous amount of work that is necessary every year to prepare this popular review. The printed version of the map in Obesity is highly cited, and the e-version is accessed ∼200, 000 times a year by ∼40, 000 unique users based mainly in academic institutions and pharmacological or biotechnology companies. Although we recognize that the yearly review in its printed and electronic versions is a valuable tool for those involved in this field, the project has become too large to be handled solely by us without support staff.

Monogenic Effects and Mendelian Disorders

Monogenics Section

The majority of disorders previously summarized in Table 2 have now been associated with a candidate gene or a genetic defect. Therefore, this year they are being merged with the monogenic obesity cases into a new table, Table 1.

Table 2. . Murine models of obesity
Mouse chromosome (cM/band)Mouse geneHuman chromosomeHuman homologGene descriptionDetailsReference
  • a

    Antisense;

  • b

    ethylnitrosourea (ENU);

  • c

    floxed;

  • d

    gene replacement;

  • e

    gene trap;

  • f

    knock-in;

  • g

    knock-out;

  • h

    spontaneous;

  • i

    overexpression;

  • j

    RNA interference;

  • k

    transgenic.

2(89)Ak20q11.2-q12ASIPAgouti. Expression limited to adipose cellsTransgene: aP2 promoter regulating expression of murine wild-type agouti cDNA Increased BW and fat mass(268, 269)
2(89)Ak20q11.2-q12ASIPAgouti, also known as BAP20 mouse. Ubiquitous expression. Unexpectedly high in skeletal muscleTransgene: human β actin promoter regulating expression of murine wild-type agouti cDNA Obesity(270)
2(89)Ak20q11.2-q12ASIPAgouti. Ubiquitous expressionTransgene: murine Pgk1 promoter regulating expression of murine wild-type agouti cDNA Obesity(270)
10(44)Abca7g19p13.3ABCA7ATP-binding cassette, subfamily A (ABC1), member 7Reduced fat and circulating high-density lipoprotein and total cholesterol in females(271)
5Acacbg12q24.1ACACBAcetyl CoA carboxylase β, also known as Acc2Reduced adiposity; resistant to diet-induced obesity(272, 273)
11(38)Acadvlg17p13-p11ACADVLAcyl-CoA dehydrogenase, very long chainLipid accumulation in myocytes; impaired temperature regulation Adult-onset fat mass gain(274, 275)
7(F4)Adam12g10q26.3ADAM12A disintegrin and metallopeptidase domain 12 (meltrin α)Moderate resistance to diet-induced obesity due to an impairment in the increase of the number of adipocytes in high-fat-fed mice(276)
16(53.4)Adamts1g21q21.2ADAMTS1A disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 1Reduced BW and adiposity(277)
17Adcyap1g18p11ADCYAP1Adenylate cyclase activating polypeptide 1Wasting; reduced adiposity(278)
11(19)Adra1bg5q23-q32ADRA1BAdrenergic receptor, α1bAccelerated weight gain on high-fat diet(279)
19(50)Adra2ak10q24-q26ADRA2ATransgene expresses adrenergic receptor α2 in adipose cellsTransgene: aP2-driven human ADRA2A cDNA When expressed in Adra3b-deficient mice, leads to obesity. When expressed in mice heterozygous for Adra3b, there is no adipose phenotype(280)
19(51)Adrb1g10q24-q26ADRB1Adrenergic receptor, β1Obesity in conjunction with mutations in Adrab2 and Adrab3(281)
19(51)Adrb1k10q24-q26ADRB1Transgene insertion 1, Susan R. Ross, expresses adrenergic receptor β1 in adipose cellsTransgene: aP2-driven expression of human ADRB1 cDNA Reduced adiposity and partially resistant to diet-induced obesity(282)
18(34)Adrb2g5q31-q32ADRB2Adrenergic receptor, β2Reduced adiposity Obesity in conjunction with targeted mutations in Adrab1 and Adrab3(281)
8(10)Adrb3g8p12-p11.2ADRB3Adrenergic receptor, β3Increased body fat. Mildly obese on chow. High obesity on high-fat diet. Obesity in conjunction with mutations in Adrab2 and Adrab3(283)
8(10)Adrb3g8p12-p11.2ADRB3Adrenergic receptor, β3Increased adiposity on chow or high-fat diets(284)
11Aebp1k7p13AEBP1AE-binding protein 1Transgene; expressed in adipose tissue; obesity in females(285)
8(D1-D2)Agrpg16q22AGRPAgouti-related proteinAge-related lean phenotype(286)
8(D1-D2)Agrpk16q22AGRPAgouti-related protein; expressed ubiquitouslyTransgene: β actin promoter regulating expression of human AGRP cDNA; elevated weight gain and obesity(287)
8(D1-D2)Agrpk16q22AGRPAgouti-related proteinTransgene. Post-embryonic deletion of AGRP-expressing neurons Lean(288)
13(16)Agtr1ag  Angiotensin II receptor, type 1aResistant to diet-induced obesity(289)
X(12.5)Agtr2gXq22-23AGTR2Angiotensin II receptor, type 2Resistant to diet-induced obesity(290)
16(15)Ahsgg3q27AHSGα-2-HS-glucoproteinResistant to diet-induced obesity(291)
1(51.7)Akp3g2q37.1ALPIAlkaline phosphatase 3, intestine, not Mn requiring; also known as IAPAccelerated weight gain on high-fat diet(292)
12(57)Akt1k14q32.3AKT1Thymoma viral proto-oncogene 1Transgene, cDNA of constitutively active Akt expressed in skeletal muscle from the human skeletal actin promoter Reduced in adiposity(293)
7(6.5)Akt2g19q13.1-13.2AKT2Thymoma viral proto-oncogene 2Reduction in adiposity, especially in young females. Age-related adipocyte loss in both sexes(294)
6Alms1g2p13ALMS1Alstrom syndrome 1 homolog (human)Gene trapped Obesity(295)
15(B1)Amacrg5p13.2-q11.1AMACRα-methylacyl-CoA racemaseReduction in BW and adiposity on phytol-supplemented diet(296)
17Angptl4g19p13.3ANGPTL4Angiopoietin like 4, also known as fasting-induced adipocyte factor (FIAF)Reduction in body fat gain upon transfer from germ-free to conventional housing(297)
9Angptl6g19p13.2ANGPTL6Angiopoietin like 6, also known as adipopoietin-related growth factor (AGF)The 20% of mice that survive development manifest obesity and insulin resistance(298)
9Angptl6k19p13.2ANGPTL6Angiopoietin like 6, also known as adipopoietin-related growth factor (AGF)Transgenic: ubiquitous expression using the chicken β-actin promoter and cytomegalovirus (CMV)-enhancer Reduced adiposity on chow and resistance to diet-induced obesity on high-fat diets(298)
7(4)Apoc1k19q13.2APOC1Apolipoprotein C1. transgene insertion 1, Louis M. Havekes-overexpressing human APOC1 geneTransgenic (Tg) mice expressing the human APOC1 gene from its own promoter Moderate reduction in adiposity relative to non-Tg mice. When crossed with the Lep background, however, Tg mice were protected against obesity and insulin resistance(299)
9(27)Apoc3g11q23.1-q23.2APOC3Apolipoprotein C-IIIObesity on high-fat diet(300, 301)
4(B1)Aqp7g9p13AQP7Aquaporin 7Increased gonadal fat pad mass(302)
4(B1)Aqp7g9p13AQP7Aquaporin 7Adult-onset obesity(303)
X(36)ArcXq11.2-q12ARAndrogen receptorFloxed gene + Cre transgene expressed from the cytomegalovirus promoter Obesity. Decreased energy expenditure(304, 305)
10(B5)Arid5bg10q21.2ARID5BAT-rich interactive domain 5B (Mrf1 like), also known as Mrf2Reduced adiposity on chow. Resistant to diet-induced obesity(306)
11(B4)Aspae17pter-p13ASPAAspartoacylase (aminoacylase) 2Reduced adiposity(307)
14(C3)Atp12ag13q12.12ATP12AATPase, H+/K+-transporting, non-gastric, α polypeptideIncreased weight loss on potassium-free diet(308)
18Atp8b1f18q21-q22ATP8B1ATPase, class I, type 8B, member 1Targeted knock-in Increased weight loss on bile salt-supplemented diet(309)
12Batfk14q24.3BATFRegulator of transcription factor B-ZIPLoss of all adipose tissue(310)
19Bbs1g11q13.1BBS1Bardet-Biedl syndrome 1 homolog (human)KO due to gene trap insertion in exon 11 Reduced BW at birth. Obesity at 10 weeks in 10% of the mutants(311)
8Bbs2g16q21BBS2Bardet-Biedl syndrome 2 homolog (human)Reduced BW at birth. Increased abdominal fat mass at 4 months(312)
9(33)Bbs4c15q22.3-23BBS4Bardet-Biedl syndrome 4 homolog (human)Low BW at weaning, adult-onset obesity after weaning(311)
9(33)Bbs4g15q22.3-23BBS4Bardet-Biedl syndrome 4 homolog (human)Low BW at weaning, adult-onset obesity after weaning(81)
2(62)Bdnfg11p13BDNFBDNF. The mutation is homozygous lethalMature-onset obesity in heterozygotes. Can be treated by food restriction(313, 314)
X(A7.1)Brs3gXq26-q28BRS3Bombesin-like receptor 3Obesity(315)
2Bub1bg15q15BUB1BBudding uninhibited by benzimidazoles 1 homolog, β (S. cerevisiae)Age-dependent loss of body fat; reduced lifespan(316)
17(34.3)C3g19p13.3C3Complement component 3; acylation-stimulating proteinFemales possess a lean phenotype and are resistant to diet-induced obesity(317, 318)
13(D1)Cartg5q13.2CARTCocaine- and amphetamine-regulated transcriptIncreased susceptibility to diet-induced obesity(319, 320)
6(A2)Cav1g7q31.1CAV1Caveolin 1Decreased adiposity; resistant to diet-induced obesity(321)
6(48.3)Cav3g3p25CAV3Caveolin 3Increased adiposity(322)
9(26)Cblg11q23.3CBLCasitas B-lineage lymphoma, also known as c-cblReduced adiposity(323)
5(34)Cckarg4p15.1-15.2CCKARCholecystokinin (CCK) A receptorResistant to CCK-mediated inhibition of food intake but normal long-term weight regulation; increased cholesterol absorption on lithogenic diet; altered thermogenic regulation(324, 325, 326)
17(28.8)Ccnd3g6p21CCND3Cyclin D3Resistant to diet-induced obesity(327)
5(2)Cd36g7q11.2CD36CD36 antigen/fatty acid translocaseAltered metabolic adaptation to dietary modulation(328)
18(6)Cdh2k18q11.2CDH2Cadherin 2, also known as N-cadherin or Ncad. Truncated gene used in this construct acts as a dominant negative alleleTransgene: expressing truncated Cdh2 using an osteoblast-specific promoter, Og2 Increased adiposity(329)
17(15.2)Cdkn1ag6p21.2CDKN1ACyclin-dependent kinase inhibitor 1A (P21)Increased adiposity(330)
6(62)Cdkn1bg12p13.1-p12CDKN1BCyclin-dependent kinase inhibitor 1B (P27)Increased adiposity(330)
7(12)Cebpag19q13.1CEBPACCAAT/enhancer-binding protein (C/EBP), αReduced adiposity(331)
7(12)Cebpad19q13.1CEBPACCAAT/enhancer-binding protein (C/EBP), αKO + gene replacement. A Cebpb knock-in was generated by replacing the entire coding region of the Cebpa locus with the Cebpb coding region Lean and resistant to diet-induced obesity(332)
2(95.5)Cebpbg20q13.13CEBPBCCAAT/enhancer-binding protein (C/EBP), βReduced adiposity(333)
16(9)Cebpdg8p11.2-11.1CEBPDCCAAT/enhancer-binding protein (C/EBP), ΔReduced adiposity(334)
13(7)Chrm3g1q41-q44CHRM3Muscarinic receptor M3Reduced adiposity(335)
18Cideag18p11.21CIDEACell death-inducing DNA fragmentation factor, α subunit-like effector AReduced adiposity and resistant to diet-induced obesity(336)
5(43)Clockb4q12CLOCKClockENU-generated mutant Obesity(337)
4(13.9)Cnr1c6q14-q15CNR1Cannabinoid receptor 1 (brain), also known as CB1 receptorFloxed gene + ubiquitously expressed Cre Reduced adiposity(338)
4(13.9)Cnr1g6q14-q15CNR1Cannabinoid receptor 1 (brain), also known as CB1 receptorOn standard chow at 20 weeks, the BWs and adiposity are 24% and 60% lower, respectively, than control mice Resistant to diet-induced obesity(339)
5Coring4p13-12CORINCorinIncreased BW(340)
8(32.6)Cpeg4q32.3CPECarboxypeptidase EKO: floxed and deleted Obesity(341)
19(2)Cpt1ag11q13.1-13.2CPT1ACarnitine palmitoyltransferase 1a, liverHomozygotes are lethal Fasting hypoglycemia in heterozygotes Increased fasting serum free fatty acids(342)
3(8)Crhk8q13CRHCorticotropin-releasing factor hormone, also known as CRF Expression of the transgene, however, is restricted to endogenous Crh-expressing cells due to a tissue-specific enhancer present within the Crh cDNA sequenceMurine corticotropin-releasing hormone cDNA expressed from the mouse metallothionein promoter Transgenic mice exhibit elevated ACTH release, high circulating levels of CRH and adrenal corticosterone. They display excess fat accumulation and muscle atrophy(343)
6(28)Crhr2g7p14.3CRHR2Corticotropin-releasing hormone receptor 2Normal adiposity on low-fat diet. Lower feed efficiency on high-fat diet (higher food intake but same weight gain as wild-type mice)(344)
9Cyb5r4g6pter-q22.33CYB5R4Cytochrome b5 reductase 4Reduced adiposity, increased food intake, hyperglycemia and hypoinsulinemia at 7 weeks(345)
9(31)Cyp19a1g15q21.1CYP19A1Cytochrome P450, family 19, subfamily a, polypeptide 1, also known as aromataseElevated gonadal fat pad weight; obesity prevented by cholesterol feeding(346, 347)
2(15.5)Dbhd9q34DBHDopamine β hydroxylase. Dopamine-deficient (DD) mice are homozygous for this mutation and also for a KO of the endogenous tyrosine hydroxylase (Th) locus. The Th knock-in in the Dbh gene restores tyrosine hydroxylase activityKO + gene replacement. A Th knock-in was generated by inserting the Th gene into the mutated Dbh locus These DD mice do not possess altered adiposity on chow diet. However, when the Th−/− and Dbh<tm2(Th)Rpa mutations are homozygous in mice that are also homozygous for the Lepob mutation, there is a significant reduction in BW and adiposity gain(348, 349)
11del(17) (p11.2)k17p11.2del(17) (p11.2)Smith-Magenis syndromeTransgenic: chromosomal rearrangement Obesity(350)
15(46.9)Dgat1g8q24.3DGAT1Acyl CoA: diacylglycerol O-acyltransferase 1Lean and resistant to diet-induced obesity(351)
15(46.9)Dgat1k8q24.3DGAT1Acyl CoA: diacylglycerol O-acyltransferase 1Transgenic; expressed in adipose cells Fatty liver but no obesity on high-fat diet(352)
15(46.9)Dgat1i8q24.3DGAT1Acyl CoA: diacylglycerol O-acyltransferase 1Adenovirus-mediated overexpression in liver Increased gonadal but not subcutaneous fat mass(353)
4(C7)Dhcr24g1p33–31.1DHCR2424-dehydrocholesterol reductaseReduction in subcutaneous and mesenteric fat(354)
12(54)Dlk1k14q32.3DLK1Δ-like 1 homolog (Drosophila), also known as Pref-1. Expressed as fusion to human immunoglobulin-γ constant region in liverTransgene. Murine cDNA expressed from albumin promoter Reduced adiposity(355)
12(54)Dlk1k14q32.3DLK1Δ-like 1 homolog (Drosophila), also known as Pref-1. Expressed as fusion to human immunoglobulin-γ constant region in adipocytesTransgene. Murine cDNA expressed from aP2 promoter Reduced adiposity(355)
14Dnajc3g13q32DNAJC3DnaJ (Hsp40) homolog, subfamily C, member 3Increased food intake; decreased adiposity(356)
1(H2)Dptg1q12-23DPTDermatopontinIncreased subcutaneous adipose number and volume(357)
16(23.3)Drd3g3q13.3DRD3Dopamine receptor 3Increased adiposity and diet-induced obesity(358)
11dup(17) (p11.2) (p11.2)k17p11.2dup(17) (p11.2) (p11.2)Smith-Magenis syndromeTransgenic: chromosomal rearrangement Obesity(350)
8(8)Eif4ebp1g8p12EIF4EBP1Eukaryotic translation initiation factor 4E-binding protein 1Reduced adiposity(359)
5Eregg4q13.3EREGEpiregulinIncreased weight loss with dextran sulfate sodium exposure(360)
19(3)Esrrag11q13ESRRAEstrogen-related receptor αReduced BW and adiposity. Resistant to diet-induced obesity(361, 362)
3(13.9)Fabp4g8q21FABP4Fatty acid-binding protein 4, adipocyteLike the control strain, homozygous mutants become obese on a high-fat diet but remain insulin sensitive(363)
3(A1-A3)Fabp5g8q21.13FABP5Fatty acid-binding protein 5, adipocyte, also known as Mal1Less adiposity than controls on high-fat diet(364, 365)
7(B2)Fgf21k19q31.1-qterFGF21Fibroblast growth factor 21Transgene. Expressed human gene in liver Resistant to diet-induced obesity(366)
2(H2)Fkhl18g20q11.1-11.2FKHL18Forkhead-like 18 (Drosophila)Resistant to diet-induced obesity(367)
7(5)FosBk19q13.32FOSBFBJ osteosarcoma oncogene BTransgene: expressing ΔFosB, an alternative spliced mRNA variant of FosB under the control of the neuron-specific enolase promoter Decreased fat mass(368, 369)
2(84)Foxa2g20p11FOXA2Forkhead box A2, also known as Hnf3b or Tcf3bKO + reporter Homozygous KO mice are embryonic lethal Heterozygotes rapidly develop obesity on a high-fat diet(370)
8(65.5)Foxc2k16q22-q24FOXC2Forkhead Box C2 expressed in adipose cellsTransgene: human FOXC2 cDNA expressed from the aP2 promoter Reduced adiposity (lipid content) on chow diet and resistance to diet-induced obesity(371, 372)
17(E5)Fshrg2p21FSHRFollicular-stimulating hormone receptorObesity(373)
6Fxyd4g10q11.21FXYD4FXYD domain-containing ion transport regulator 4Increased food intake but reduced BW(374)
19(2)Galg11q13.2GALGaleninExaggerated obesity in NPY-deficient mice(375)
10(43)Gamtg19p13.3GAMTGuanidinoacetate methyltransferaseDecreased adiposity(376)
8(5)Gas6g13q34GAS6Growth arrest specific 6Resistant to diet-induced obesity(377)
11(60)Gastg17q21GASTGastrinObesity(378)
11(E2)Gcgrg17q25GCGRGlucagon receptorDecreased white and brown adipose mass(379)
11(1)Gckk7p15.3-p15.1GCKGlucokinase. Expressed in skeletal muscleTransgene. Murine Gck cDNA expressed from the murine myosin light-chain 1 promoter Resistant to diet-induced obesity(380)
11(1)Gckk7p15.3-p15.1GCKGlucokinase. Expressed in liverTransgene. Murine Gck cDNA expressed from the murine Pepck promoter Increased weight gain on a high-fat diet(381)
6(60.6)Gdf3i12p13.1GDF3Growth differentiation factor 3Adenovirus-mediated overexpression Increase in BW and adiposity on high-fat diet but no phenotype on chow(382)
1(27.8)Gdf8g2q232.2GDF8Growth differentiation factor 8, also known as myostatinReduced adiposity and increased muscle mass Loss of Gdf8 expression also results in a significant reduction in adipose mass accumulation in agouti lethal yellow (Ay) and Lepob mutants(383, 384)
1(27.8)Gdf8k2q232.2GDF8Growth differentiation factor 8, also known as myostatinTransgene Overexpressed in muscle Resistant to diet-induced obesity(385)
6(35.5)Gfpt1k2p13GFPT1Glutamine fructose-6-phosphate transaminase 1Transgene Overexpressed in adipose cells Increased adiposity(386)
14(D3-E1)Gfra2g8p21GFRA2Glial cell line-derived neurotrophic factor family receptor α2Growth retardation accompanied by reduced fat mass and elevated basal metabolic rate(387)
11(65)Ghk17q24.2GHGrowth hormone (GH)Transgene. Bovine GH overexpressed from metallothionein promoter Resistant to diet-induced obesity(388)
11(65)Ghk17q24.2GHGrowth hormone (GH)Transgene. Bovine GH expressed in central nervous system Obese(389)
15(4.6)Ghrf5p13-12GHRGrowth hormone (GH) receptorKnock-in. Independent deletion of two domains designated m569 and m391 Increased adiposity in males(390)
2(89)Ghrhk20q11.2GHRHGrowth hormone (GH)-releasing hormoneTransgenic mouse expressing human GHRH cDNA from the mouse metallothionein I promoter Increased adiposity(391)
6(E3)Ghrlg3p26-p25GHRLGhrelinKO (lacZ fusion) On a high-fat diet, homozygous mutants tend to have a decrease in percentage body fat and an increase in percentage lean body mass without any significant difference in BW compared with wild-type mice(392)
3Ghsrg3q26.31GHSRGrowth hormone (GH) secretagogue receptorDecreased BW(393)
3Ghsrk3q26.31GHSRGrowth hormone (GH) secretagogue receptor Expression limited to GHRH (GH-releasing hormone-expressing neurons)Transgene. Rat GHRH 5′ and 3′ genomic sequences driving expression of human GHSR cDNA Decreased BW and adiposity(394)
7Giprg19q13.3GIPRGastric inhibitory polypeptide receptorResistant to diet-induced obesity; reduced adiposity in aged mice; lower respiratory exchange ratio and higher fat oxidation in the light phase(395, 396, 397)
2(104)Gnasg20q13.2-q13.3GNASImprinted locus GNAS (guanine nucleotide-binding protein, α-stimulating) complex locusKO (exon 2) Loss of maternal expression leads to obesity, with increased lipid per cell in white and brown adipose tissue, whereas loss of paternal expression leads to a lean phenotype, with decreased lipid in adipose tissue(398, 399)
2(104)Gnasg20q13.2-q13.3GNASImprinted locus GNAS (guanine nucleotide-binding protein, α-stimulating) complex locusKO (exon 1) Maternal inheritance of the mutant allele gives larger BW in heterozygous mice(400)
19(4)Gng3g11p11GNG3Guanine nucleotide-binding protein (G-protein), γ3 subunitKO. Floxed and deleted Female homozygotes have reduced inguinal and retroperitoneal fat pads(401)
19(52)Gpamg10q25.2GPAMGlycerol-3-phosphate acyltransferase, mitochondrialReduced BW and adiposity(402)
2(33)Gpd2g2q24.1GPD2Glycerol phosphate dehydrogenase 2, mitochondrialReduced BW and adiposity(403)
2(33)Gpd2g2q24.1GPD2Glycerol phosphate dehydrogenase 2, mitochondrialEnhanced adipose and BW gain of females on a high-fat diet. This effect was not observed in males(404)
12Gphb5k14q23.2GPHB5Glycoprotein hormone β5, also known as GPB5 and OGHTransgene. Ubiquitous Resistant to diet-induced obesity(405)
19Gpr10g10q26.13GPR10G-protein-coupled receptor 10Adult-onset obesity(406)
5(F)Gpr109ag12q24.31GPR109AG-protein-coupled receptor 109aAbsence of nicotinic acid-induced inhibition of free fatty acid release from adipocytes(407)
15Gpr24g22q13.3GPR24G-protein-coupled receptor 24, also known as Mch1rLean and resistant to diet-induced obesity(408)
7Gpr40g19q13.1GPR40G-protein-coupled receptor 40Resistant to diet-induced obesity-mediated changes(409)
1(A1)Gpr7g8p22-q21.13GPR7G-protein-coupled receptor 7Adult-onset obesity(410)
9(57)Gpx1k3p21.3GPX1Glutathione peroxidase 1Transgene consisting of complete genomic Gpx1 gene Increased BW and adiposity(411, 412)
7Grm5g11q14.3GRM5Glutamate receptor, metabotropic 5Lower BW and reduced adipose gain on high-fat diet(413)
6(A3)Grm8g7q31.3-q32.1GRM8Glutamate receptor, metabotropic 8Increased fat mass(414)
16(B4)Gsk3bk3q13.3GSK3BGlycogen synthase kinase 3βTransgene expressing human cDNA in skeletal muscle Increased BW and adiposity in male transgenic mice(415)
6(48.7)Gt(ROSA)26Sork UnknownGene trap ROSA 26, Philippe SorianoTransgene. Conditional activation of Akt in skeletal muscle Decreased adipose mass and increased muscle mass after treatment with tamaxiphen(293)
10(43)Gtrgeo22e19p13.3C19orf20Gene trap 22, Philippe SorianoReduced BW and adiposity(416)
11(61.2)Hcrtk17q21HCRTHypocretin (orexin). Loss of orexin-containing neuronsTransgene. Expression of Mjd (Ataxin 3) with expanded repeats in orexinergic neurons Late-onset obesity (C57BL/6J and DBA/2 mixed genetic background)(417)
11(61.2)Hcrtk17q21HCRTHypocretin (orexin). Loss of orexin-containing neuronsTransgene. Expression of Mjd (Ataxin 3) with expanded repeats in orexinergic neurons No weight difference between mutant and wild type when both on a C57BL/6J genetic background(418)
2(71)Hdcg15q21-q22HDCHistidine decarboxylaseIncreased BW and adiposity(419)
5(20)Hdhk4p16.3HDHuntington disease (HD) gene homolog, also known as Huntington, R6/2Transgenic. Human exon 1 of the HD gene carrying ∼141 to 157 CAG repeats expressed from the endogenous HD gene promoter Despite an overall growth retardation, the transgenic mice have increased adiposity Adult-onset wasting syndrome(420)
13(46)Hexbg5q13HEXBHexosaminidase BLean(421)
10(67.5)Hmga2g12q15HMGA2High mobility group AT-hook 2Resistant to diet-induced obesity(422)
6(49)Hrh1g3p25HRH1Histamine receptor H1Late-onset obesity(423)
2Hrh3g20q13.3HRH3Histamine receptor H3Increased adiposity and BW(424)
1Hsd11b1g1q32-q41HSD11B1Hydroxysteroid 11-β dehydrogenase 1Resistant to diet-induced obesity(425)
1Hsd11b1k1q32-q41HSD11B1Hydroxysteroid 11-β dehydrogenase 1Transgenic. Promoter aP2-specific expression Increased adiposity(426)
8(50.8)Hsd11b2k16q22HSD11B2Hydroxysteroid 11-β dehydrogenase 2Transgenic. Human gene expressed in adipose cells Resistant to diet-induced obesity(427)
X(66)Htr2cgXq24HTR2C5-Hydroxytryptamine (serotonin) receptor 2CLate-onset obesity(428)
9(7)Icam1g19p13.2ICAM1Intercellular adhesion molecule-1Late-onset obesity Accelerated adiposity on a high-fat diet (N4 mice)(429)
9(7)Icam1g19p13.2ICAM1Intercellular adhesion molecule-1Transient increased adiposity after 11 days of high-fat diet but reduced BW and adiposity relative to controls after 50 days of high-fat diet (N8 mice)(430)
9(7)Icam1k19p13.2ICAM1Intercellular adhesion molecule-1 (ICAM-1)Transgene. Expressing soluble ICAM-1 in liver Increased weight gain on a Western-type diet(431)
1(29.8)Idh1k2q33.3IDH1Isocitrate dehydrogenase 1 (NADP+), soluble, also known as IDPc Expression limited to liver and adipose tissueTransgene, Idh1 cDNA expressed from the rat cytosolic Pepck promoter Obesity(432)
12(21.5)Ifrd1k7q22-q31IFRD1Also known as Tis7, interferon-related developmental regulator 1Transgene. Expressed in gut small intestine Increased adiposity(433)
15Igfbp6k12q13IGFBP6Insulin-like growth factor-binding protein 6Transgene (human). Expressed in glial cells Down-regulation of uncoupling protein 1(434)
2(10)Il1rng2q14.2IL1RNInterleukin 1 receptor antagonistReduced BW(435)
2(10)Il1rng2q14.2IL1RNInterleukin 1 receptor antagonistReduced adiposity, resistant to diet-induced obesity and resistant to obesity due to monosodium glutamate treatment(436)
5(17)Il6g7p21IL6Interleukin 6Increased adiposity and BW(437)
5(17)Il6g7p21IL6Interleukin 6No effect on adiposity. Reduced BW in 3-month-old mice(438)
7(F1)Inppl1g11q23INPPL1Polyphosphate phosphatase-like 1 (SHIP-2)Resistant to diet-induced obesity(439)
8(1)Insrc19p13.3-p13.2INSRInsulin receptor not expressed in muscle cellsFloxed gene and muscle-specific Cre expression Increased adipose depots and obesity(440)
8(5)Irs2c13q34IRS2Insulin receptor substrate 2. Conditional KO in pancreatic β cells and hypothalamusFloxed gene + Cre transgene expressed from the rat insulin promoter Fat mass, increased(441)
8(5)Irs2c13q34IRS2Insulin receptor substrate 2. Conditional KO in pancreatic β cells and hypothalamusFloxed gene + Cre transgene expressed from the rat insulin promoter Fat mass, increased(442)
3(52)Kcna3g1p13.3KCNA3Potassium voltage-gated channel, shaker-related subfamily, member 3, also known as Kv1.3Reduced BW and resistant to diet-induced obesity(443)
7(41)Kcnj11g11p15.1KCNJ11Potassium inwardly rectifying channel, subfamily J, member 11, also known as Kir6.2Increased BW (10%) and epididymal fat pad (70%) weight(444)
14(E2.1)Klf5g13q22.1KLF5Kruppel-like factor 5Deficiency in white adipose tissue development(445)
6(10.5)Lepk7q31.3LEPMouse Lep cDNA was cloned 3′ of the liver-specific Apoe promoter and 5′ of liver-specific enhancer sequence. Serum leptin expression is 200- to 300-fold higher than in wild-type miceTransgene: Apoe promoter expressing murine leptin cDNA Absence of fat pads(446)
6(10.5)Lepk7q31.3LEPThis transgene consists of a mouse Lep cDNA fused to the human APCS promoter with hormone expression targeted to the liver. In mutants carrying 30 copies of the transgene serum, leptin expression is about 12-fold higher than in wild-type miceTransgene: human APCS promoter expressing murine leptin cDNA Decreased BW. Absence of adipose tissue(447)
4(46.7)Leprf1p31LEPRSelective loss of long form of leptin receptorObesity(448)
4(46.7)Leprk1p31LEPRTransgene insertion 1, Gerard Karsenty. An isoform of Lepr cDNA lacking the transmembrane domain found in all other isoforms was cloned 3′ of the liver-specific Apoe promoter and 5′ of liver-specific enhancer sequenceTransgene: Apoe promoter expressing murine-soluble leptin receptor cDNA Mice carrying this transgene possess normal body fat. However, in mice heterozygous for the lepob mutation, the transgenic mice show significantly increased adiposity(446)
4(46.7)Leprc1p31LEPRNeuronal-specific deletion of leptin receptorFloxed gene + Cre transgene expressed from the Syndecan 1 promoter Obesity(449, 450)
4(46.7)Leprk1p31LEPRLeptin receptor. Mutation due to insertion of rabbit smooth muscle myosin heavy chain promoter regionMutation due to transgene insertion Obesity(451)
4(46.7)Leprk1p31LEPRLeptin receptorTransgenic: neuron-specific expression Rescue of obesity of Leprdb mutant mice(452)
4(46.7)Leprk1p31LEPRLeptin receptorTransgenic: neuron-specific expression (50% and 75%) Adiposity and obesity are proportional to hypothalamic LEPR deficiency, but fertility and cold tolerance remain intact(449)
7(23)Lhbk19q13.32LHBLuteinizing hormone β polypeptideObesity in females(453)
19Lip1g10q23.2-q23.3LIPALysosomal acid lipase 1Decreased BW, fatty liver, loss of brown and white fat depots; ectopic fat deposition into liver, spleen, and bowel(454, 455)
9(39)Lipcg15q21-23LIPCLipase, hepaticKO with background strain effects Increased adiposity mediated by background susceptibility(456)
7(5.5)Lipeg19q13.2LIPELipase, hormone sensitiveReduced fat pad size, heterogenous adipocyte size, increased brown fat. Resistant to diet-induced obesity(457, 458)
7(5.5)Lipek19q13.2LIPELipase, hormone sensitiveTransgene; human LIPE expressed in adipose tissue Corrects adipose defects of Lipe-deficient mice(459)
12(9)Lpin1h2p25.1LPIN1Lipin 1, gene responsible for phenotype of fatty liver dystrophic mouseSpontaneous null allele Reduced adiposity on chow. Resistant to diet-induced obesity(460)
12(9)Lpin1k2p25.1LPIN1Lipin 1Transgene. Expressed in adipose tissue Obesity due to increased fat storage(461)
12(9)Lpin1k2p25.1LPIN1Lipin 1Transgene. Expressed in skeletal muscle Obesity due to changes in energy expenditure(461)
7(61)Mapk3g6p12-p11.2MAPK3Mitogen-activated protein kinase 3, also known as ERK1, Prkm3, p44N6 mice. Reduced adiposity, resistant to diet-induced obesity(462)
2(E1)Mapk8ip1g11p11.2MAPK8IP1Mitogen-activated protein kinase 8 interacting protein 1. Acts as an inhibitor of c-Jun N-terminal kinaseReduced adiposity(463, 464)
2(100)Mc3rg20q13.2-q13.3MC3RMelanocortin receptor 3Obesity(465)
2(100)Mc3rg20q13.2-q13.3MC3RMelanocortin receptor 3Obesity(466)
18(E1)Mc4rg18q22MC4RMelanocortin receptor 4Obesity(467)
18(E1)Mc4rk18q22MC4RMelanocortin receptor 4Transgene. Expressed in paraventricular hypothalamic nucleus and subpopulation of amygdala Prevents 60% of obesity, rescues hyperphagia but not reduced energy expenditure of Mc4r-deficient mutant mice(468)
6(7.5)Mestk7q32MESTMesoderm-specific transcriptTransgene. Expressed in adipose tissue Increased adiposity(469)
2Mkksg20p12MKKSMcKusick-Kaufman syndrome proteinObesity(470)
5Mlxiplg7q11.23MLXIPLMLX interacting protein-likeLean; rapid death on high-sucrose and high-fructose diets(471)
10(40.9)Mmp11g22q11.23MMP11Matrix metalloproteinase 11Obesity(472)
10(70)Mmp19g12q14MMP19Matrix metalloproteinase 19Accelerated BW and adipose mass gain on a high-fat diet(473)
8(45)Mt1, Mt2g16q13MT1AMetallothionein I and IIKO; both mutations generated with the same targeting construct Increased BW. Adult-onset obesity(474, 475)
15(32)Myck8q24.12-q24.13MYCMyelocytomatosis oncogene. Expression limited to liverTransgene. Murine c-myc expressed under the control of the Pepck promoter Resistant to diet-induced obesity(476)
9Ncb5org6pter-q22.33NCB5ORNADPH cytochrome B5 oxidoreductaseReduced adipose mass(345)
3Nhlh2g1p12-p11NHLH2Nescient helix loop helix 2, also known as neural transcription factor 2 or NSCL2Adult-onset obesity(477)
5Nmug4q12NMUNeuromedin UElevated BW and obesity(478)
5Nmuk4q12NMUNeuromedin UTransgene. Expressed ubiquitously Lean and hypophagic(479)
11(45.6)Nos2g17q11.2-12NOS2ANitric oxide synthase 2, inducible, macrophage, also known as iNOSReduced adiposity(480)
11Npbg17q25.3NPBNeuropeptide B; ligand for GPR7Mild obesity(481)
6(26)Npyg7p15.1NPYNeuropeptide YNo obesity phenotype except with Galenin (Gal) KO(375)
 Npy−/− + Gal−/−g  Double homozygote for neuropeptide Y and galenin deficiencyKO: compound double homozygous mutant strain Obesity(375)
8(33)Npy1rg4q31.3-q32NPY1RNeuropeptide Y receptor Y1Obesity(482)
8(32.5)Npy5rg4q31-q32NPY5RNeuropeptide Y receptor Y5Increased adiposity leading to mild adult-onset obesity(483)
7Nr1h2g19q13.3-13.2NR1H2Nuclear receptor subfamily 1, group H, member 2, also known as LXR βReduced adiposity(484)
1(92.6)Nr1i3g1q23.3NR1I3Nuclear receptor subfamily 1, group I, member 3Accelerated adipose loss on calorie-restricted diet(485)
18(20)Nr3c1c5q31NR3C1Nuclear receptor subfamily 3, group C, member 1; also known as glucocorticoid receptorFloxed gene and rat nestin-driven Cre Neuronal-specific ablation leads to increased adiposity preweaning, leading to reduced adiposity in older mice due to altered food intake and metabolic efficiency(486)
2(107)Ntsr1g20q13-20q13NTSR1Neurotensin receptor 1Adult-onset increase in BW and adiposity(487)
10(8)Oprm1g6q24-q25OPRM1Opioid receptor, μ1, also known as MOR, MOR-1Resistant to diet-induced obesity(488)
1(98.6)Parp1g1q41-q42PARP1ADP-ribosyltransferase [NAD+, poly(ADP-rose)polymerase] 1, also known as Adprt1 or AdprpAge-onset obesity in a mixed genetic background(489, 490)
13(44)Pcsk1g5q15-q21PCSK1Proprotein convertase subtilisin/kexin type 1Increased adipose mass in heterozygous mice(491)
XPcsk1nkXp11.23PCSK1NProprotein convertase subtilisin/kexin type 1 inhibitorTransgene: expressing Pcsk1n cDNA using the β-actin promoter Adult-onset obesity(492)
7(6.5)Peg3g19q31.4PEG3Paternally expressed 3, also known as Zfp102, End4, Pw1Obesity(493)
11(31)Pemtg17p11.2PEMTPhosphatidylethanolamine N-methyltransferaseLiver abnormalities on high-fat diet(494, 495)
13(50)Pik3r1g5q13.1PIK3R1Phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85α)Smaller adipocytes and reduced adiposity(496)
11(58.2)Pip5k2be17q12PIP5K2BPhosphatidylinositol-4-phosphate 5-kinase, type II, βReduced BW and adiposity; resistant to diet-induced obesity(497)
5(F1/G1)Pla2g1bg12q23-q24.1PLA2G1BPhospholipase A2, group IB, pancreasNormal BW and fat pad weight on chow diet; resistant to diet-induced obesity when fed a western diet. KO mice also displayed increased lipid content in the stool, thus displaying decreased fat absorption(498)
7Pling15q26PLINPerilipinReduced adiposity. Resistance to diet-induced obesity(499)
9Plscr1g3q23PLSCR1Phospholipid scramblase 1Elevated adiposity(500)
11(43)Plscr3e17p13.1PLSCR3Phospholipid scramblase 3Elevated BW and adipose mass(501)
10(47)Pmchg12q23-q24.1PMCHPromelanin-concentrating hormone, also known as MCHReduced BW and adiposity; resistant to diet-induced obesity(502, 503)
12(4)Pomc1g2p23.3POMCPro-opiomelanocortin-αObesity on chow and high-fat diets(504, 505)
5(75)Porg7q11.2PORP450 (cytochrome) oxidoreductaseConditional KO (liver specific) Increased liver weight and fatty liver(506, 507)
15(48.8)Pparag22q13.31PPARAPeroxisome proliferator-activated receptor αModerate elevation in gonadal fat in chow-fed females; significant increase in adiposity relative to wild-type mice in both males and females in high-fat diet-fed mice(508)
15(48.8)Pparak22q13.31PPARAPeroxisome proliferator-activated receptor αTransgene. Expressed in muscle Resistant to diet-induced obesity(509)
17(13.5)Ppardc6p21.2-p21.1PPARDPeroxisome proliferator activator receptor Δ, also known as peroxisome proliferator-activated receptor β. Specific loss of Ppard from adipose cellsFloxed gene and aP2-driven Cre Resistant to diet-induced obesity and reduced adiposity in Leprdb homozygous mutants(510)
17(13.5)Ppardc6p21.2-p21.1PPARDPeroxisome proliferator activator receptor Δ, also known as peroxisome proliferator-activated receptor β, overexpressed in skeletal muscleFloxed transgene. Cre-Lox strategy to overexpress Ppard in skeletal muscle using HAS-Cre Reduction in fat mass and adipocyte cell size(511)
17(13.5)Ppardg6p21.2-p21.1PPARDPeroxisome proliferator activator receptor Δ, also known as peroxisome proliferator-activated receptor βOn a high-fat diet, KO mice develop greater adiposity than controls despite a lower overall total BW(512)
6(52.7)Ppargc3p25PPARGLoss of peroxisome proliferator-activated receptor γ from adipose cellsFloxed gene and aP2-driven Cre Reduced adiposity and resistant to diet-induced obesity(513, 514)
6(52.7)Ppargc3p25PPARGLoss of peroxisome proliferator-activated receptor γ from muscleFloxed gene and muscle creatine kinase (MCK)-driven Cre Increased adiposity(515)
6(52.7)Ppargc3p25PPARGLoss of peroxisome proliferator-activated receptor γ from β cellsFloxed gene and rat insulin promoter-driven Cre Attenuated β cell hyperplasia in response to a high-fat diet(516)
6(52.7)Ppargc3p25PPARGPeroxisome proliferator-activated receptor γKO + reporter Selective loss of PPARg2 isoform leads to reduced BW, smaller adipocytes, and resistance to diet-induced obesity(517)
6(52.7)Ppargf3p25PPARGPeroxisome proliferator-activated receptor γKnock-in expressing dominant negative allele Lethal in homozygotes. Heterozygotes are lean and resistant to diet-induced obesity(518)
5(C1)Ppargc1ag4p15.1-15.2PPARGC1APeroxisome proliferative-activated receptor, γ, coactivator 1αResistant to diet-induced obesity; cold sensitive(519)
5(C1)Ppargc1ag4p15.1-15.2PPARGC1APeroxisome proliferative-activated receptor, γ, coactivator 1αIncreased adiposity in young females and old males(520)
18Ppargc1bk5q32PPARGC1BPeroxisome proliferative-activated receptor, γ, coactivator 1βTransgene. Murine cDNA expressed from the chicken β-actin promoter Resistant to diet-induced obesity(521)
6(A2)Ppp1r3ag7q31.1PPP1R3AProtein phosphatase 1, regulatory (inhibitor) subunit 3AIncreased BW and obesity(522)
19(C3)Ppp1r3cg10q23-q24PPP1R3CProtein phosphatase 1, regulatory (inhibitor) subunit 3C, also known as PTGHomozygous mutants are embryonic lethal. Heterozygotes show increased intramyocellular lipid stores and elevated circulating leptin, triglycerides, and free fatty acids(523)
11Ppyk17q21PPYPancreatic polypeptideTransgenic. Mouse Ppy cDNA expressed from the chicken β-actin hybrid promoter Reduced BW and adiposity(524, 525)
4Prkaa2g1p31PRKAA2Protein kinase, adenosine monophosphate-activated, α2 catalytic subunit. No expression in adipocytesKO. Floxed gene + aP2 expressed Cre Increased adiposity(526)
1Prkag3k2q35PRKAG3Transgene insertion 1, Leif Andersson. Expression of the mutated protein was seen in the skeletal muscle. Levels of the endogenous PRKAG3 protein were reduced, resulting in no significant change in overall PRKAG3 protein expressionAn Myl1 promoter and enhancer expressing a full-length mouse Prkag3 cDNA (encodes protein kinase, AMP-activated, γ3, noncatalytic subunit) with a single missense mutation (R225Q) Transgenic mice have lowered adiposity and are protected against high-fat diet-induced triglyceride accumulation and insulin resistance(527)
12(B1)Prkar2bg7q22PRKAR2BProtein kinase, cAMP-dependent regulatory, type IIβ, also known as RIIβDecreased adiposity; resistant to diet-induced obesity(528, 529)
2(2)Prkcqk10p15PRKCQProtein kinase C, θObesity(530)
19Prkhrg10q26.13PRLHRProlactin-releasing hormone receptorObesity(406)
1(106.3)Prox1g1q32.2-q32.3PROX1Prospero-related homeobox 1Obesity in heterozygotes(531)
2(H3)Ptpn1g20q13.1-q13.2PTPN1Protein tyrosine phosphatase, non-receptor type 1Reduced adiposity(532, 533)
5(F1/G1)Ptpn11g12q24PTPN11Protein tyrosine phosphatase, non-receptor type 11Forebrain-specific KO Obesity(534)
2(73.1)Ptpns1g20p13PTPNS1Protein tyrosine phosphatase, non-receptor-type substrate 1, also known as SHPS-1Decreased BW and fatty livers(535)
11Pttg1g5q35.1PTTG1Pituitary tumor-transforming 1Reduced BW and cessation of weight gain after 6 months in males accompanied by loss of epididymal fat mass(536)
11(B2)Rai1g17p11.2RAI1Retinoic acid induced 1Homozygote lethal. Heterozygotes are obese(537)
9(50)Rasgrf1g15q24RASGRF1RAS protein-specific guanine nucleotide-releasing factor 1Reduced BW and adiposity(538)
1(69.9)Ren1k1q32RENRenin 1Transgene: human REN gene expressed from endogenous promoter Late-onset obesity(539)
8(0.4)Retnk19p13.2RETNResistin/ADSF/Fizz3. Adipocyte-specific overexpression of dominant negative RetnTransgene: aP2 promoter expressing Retn fused to the human IgGγ constant region Increased adiposity but enhanced glucose disposal and insulin sensitivity(540)
16(33)Retnlbk3q13.1RETNLBResistin-like β expressed in liverHyperlipidemia and fatty liver on high-fat diet(541)
X(65.7)Rps6ka3gX p22.2-p22.1RPS6KA3Ribosomal protein S6 kinase polypeptide 3Reduced BW and adiposity; resistant to diet-induced obesity(542)
11Rps6kb1g17q23.2RPS6KB1Ribosomal protein S6 kinase, polypeptide 1, S6K1Resistant to diet-induced obesity(543)
4Rsc1a1g1p36.1RSC1A1Regulatory solute carrier protein, family 1, member 1Obesity(544)
1(88.1)Rxrgg1q22-q23RXRGRetinoid X receptor γResistant to diet-induced obesity(545)
19(43)Scd1g10SCD1Stearyl-CoA desaturase 1Reduced BW and adiposity; resistant to diet-induced obesity(508, 546)
12(1)Sdc1k2p24.1SDC1Syndecan 1Transgenic. Mouse Sdc1 cDNA expressed from the cytomegalovirus promoter/enhancer Adult-onset obesity(547)
4(60.8)Sdc3g1pter-p22.3SDC3Syndecan 3Reduced adiposity on chow. Resistant to diet-induced obesity(548)
5Serpine1g7q21.3-q22SERPINE1Serine (or cysteine) proteinase inhibitor, clade E, member 1, also known as plasminogen activator inhibitor, type IResistant to diet-induced obesity(549)
5Serpine1g7q21.3-q22SERPINE1Serine (or cysteine) proteinase inhibitor, clade E, member 1, also known as plasminogen activator inhibitor, type ISame BW gain as control mice on high-fat diet. No difference in subcutaneous fat mass but elevated gonadal adipose mass. Mutant and litter mates are 80% B6 and 20% 129 composite(550)
5Serpine1k7q21.3-q22SERPINE1Serine (or cysteine) proteinase inhibitor, clade E, member 1, also known as plasminogen activator inhibitor, type I. Expressed in adipose cellsTransgene. Murine cDNA expressed from the aP2 promoter Resistant to diet-induced obesity(551, 552)
8(9.5)Sfrp1g8p12-p11.1SFRP1Secreted frizzled-related sequence protein 1KO + reporter Reduced adiposity in males(553)
7(61)Sh2bpsm1g16p11.2SH2BSH2-B PH domain-containing signaling mediator 1, also known as SH2-BObesity(554)
10(26.5)Sim1c6q16.3-q21SIM1Single-minded 1Floxed gene and EIIa-expressed Cre Obesity in heterozygous mice(555)
10(26.5)Sim1g6q16.3-q21SIM1Single-minded 1Obesity in heterozygous mice(556)
11(40)Slc2a4g17p13SLC2A4Solute carrier family 2 (facilitated glucose transporter), member 4 (encodes GLUT4)Reduced adiposity(557)
11(40)Slc2a4k17p13SLC2A4Solute carrier family 2 (facilitated glucose transporter), member 4 (encodes GLUT4)Transgene. Expressed in adipose tissue Increased fat mass(558)
6Slc6a1k3p25-p24SLC6A1γ -aminobutyric acid transporter ITransgenic. Mouse Slc6a1 brain-derived cDNA expressed from the cytomegalovirus promoter/enhancer Obesity(559)
15(31.7)Soat2g12q13.13SOAT2Sterol O-acyltransferase 2Resistant to fatty liver but elevated circulating triglycerides and high-density lipoprotein cholesterol(560)
11(E2)Socs3c17q25.3SOCS3Suppressor of cytokine signaling 3. Cerebrum- and hypothalamus-specific loss of Socs3Floxed gene + transgenic Cre expressed from rat nestin promoter Decreased BW and resistant to diet-induced obesity(561)
11(E2)Socs3c17q25.3SOCS3Suppressor of cytokine signaling 3. Cerebrum and hypothalamus-specific loss of Socs3Floxed gene + transgenic Cre expressed from Syndecan I promoter Decreased BW and resistant to diet-induced obesity(561)
17(8)Sox8g16p13.3SOX8SRY box-containing gene 8Decreased fat mass(562)
11(29.9)Sparcg5q31.3-q32SPARCSecreted acidic cysteine-rich glycoprotein (osteonectin)Increased adiposity with no effect on BW(563)
11Srebf1k17p11.2SREBF1Transgene expresses sterol regulatory element-binding factor 1 in adipose cellTransgene: aP2-driven human SREBF1c cDNA Reduced BW and adiposity(564)
11Srebf1k17p11.2SREBF1Sterol regulatory element-binding factor 1, transcript 1a, also known as Srebp1. Expressed in adipose cellsTransgene expressing the human SREBF1–1a cDNA using the murine aP2 promoter Adipocyte hypertrophy and fatty liver(565)
11Srebf1k17p11.2SREBF1Sterol regulatory element-binding factor 1, transcript 1c, also known as Srebp1. Expressed in adipose cellsTransgene expressing the human SREBF-1c cDNA using the murine aP2 promoter Loss of all adipose tissue(564)
11(60.5)Stat3c17q21.31STAT3Pancreatic- and hypothalamic-specific deletion of Stat3; signal transducer and activator of transcription 3Floxed gene + Cre transgene expressed from the rat insulin II promoter Obesity. Transplantation of wild-type pancreatic islets into the mutants did not alleviate obesity, suggesting that lack of hypothalamic Stat3 expression is responsible for the obesity(566)
11(60.5)Stat3c17q21.31STAT3Neuronal-specific deletion of Stat3; signal transducer and activator of transcription 3Floxed gene + Cre transgene expressed from the rat Nestin promoter Obesity(567)
11(60.5)Stat5bg17q11.2STAT5BSignal transducer and activator of transcription 5BIncreased adiposity(568)
7(6.5)Tgfb1k19q13.31TGFB1Transforming growth factor, β 1Transgenic. Human TGFB1 cDNA expressed from the rat PEPCK promoter Reduced adiposity; lipodystrophy(569)
11(57)Thrag17q11.2THRAThyroid hormone receptor αKO; gene replacement with dominant negative mutant allele Increased BW and adiposity(570)
14(B1)Tktg3p14.3TKTTransketolaseHomozygous mutants are embryonic lethal. Heterozygotes display reduced BW and adiposity(571)
17(19.1)Tnfg6p21.3TNFTNFReduction in BW and adiposity(572)
17(19.1)Tnfk6p21.3TNFTNF. Non-cleavable mutant protein expressed in TNF-deficient miceElevated BW and adipose fat mass(573)
7(51.5)Tubg11p15.5TUBTubby candidate geneLate-onset obesity(574)
3(47.1)Txnipg1q21.1TXNIPThioredoxin-interacting proteinIncreased fat-to-muscle ratio(575)
2(67.4)Ubr1g15q13UBR1Ubiquitin protein ligase E3 component n-recognin 1Lean(576)
8(38)Ucp1g4q28-q31UCP1Uncoupling protein 1, mitochondrialTemperature-dependent resistance to diet-induced obesity on C57BL/6J genetic background(577)
8(38)Ucp1k4q28-q31UCP1Transgene insertion 1, Frederic Bouillaud. The transgene consists of a rat uncoupling protein 1 (UCP1) cDNA sequence under the control of a mouse Ckmm promoter. Expression limited to skeletal and cardiac muscleTransgene: murine muscle creatine kinase promoter expressing rat UCP1 cDNA Lower BW and reduced adiposity(578)
8(38)Ucp1k4q28-q31UCP1Uncoupling protein 1 (UCP1), mitochondrialTransgene. UCP1 promoter expressing the diphtheria toxin gene Ablation of UCP1 expressing tissues leads to obesity(579, 580)
7(50)Ucp2/Ucp3k11q13UCP2/UCP3Uncoupling protein 2 (UCP2), mitochondrial; uncoupling protein 3 (UCP3), mitochondrialTransgene. Murine bacterial artificial chromosome containing the genomic UCP2 and UCP3 genes Reduced adiposity(581)
7(50)Ucp3k11q13UCP3Uncoupling protein 3 (UCP3), mitochondrial. Expression limited to skeletal muscleTransgene. Murine UCP3 cDNA expressed from the mouse Mck promoter No difference on chow, but a 4-week exposure to a high-fat diet revealed transgenic mice have less weight gain and reduced adipose gain(582)
3(68.5)Unc5ck4q21-q23UNC5Cunc-5 homolog C (C. elegans)KO/transgene: a cDNA encoding telomerase reverse transcriptase under the control of the chicken β-actin promoter randomly inserted into intron 1 of Unc5c Reduction in BW and adiposity(583)
5(79)Vgfg7q22VGFVGF nerve growth factor inducibleReduction in BW and adiposity(584)
19(20)Vldlrg9p24VLDLRVery-low-density lipoprotein receptorReduction in BW and adiposity(585)
5Wbscr14g7q11.23WBSCR14Williams-Beuren syndrome chromosome region 14 homolog (human)Lower adiposity on standard diet. Rapid death on feeding a high-fructose or high-sucrose diet(471)
15(56.8)Wnt10bk12q13WNT10BWingless-related MMTV integration site 10bTransgene, cDNA expressed from the aP2 (Fabp4) promoter Reduced adiposity and resistant to diet-induced obesity. Loss of brown adipose tissue(586, 587)
15(56.8)Wnt10bg12q13WNT10BWingless-related MMTV integration site 10bIncreased muscular adiposity(588)
7(10.2)Zfp36g19q13.1ZFP36Zinc finger protein 36Reduction in BW and adiposity(589)
Table 1. . Single-gene and obesity-related Mendelian disorders
OMIM no.SyndromeLocusCandidate geneReference
Single-gene mutations with an obesity phenotype    
 122561Corticotropin-releasing hormone receptor 117q12-q22CRHR1(14)
 602034Corticotropin-releasing hormone receptor 27p14.3CRHR2(14)
 601751G-protein-coupled receptor 2422q13.2GPR24(15)
 164160Leptin (obesity homolog, mouse)7q31.3LEP(16, 17, 18, 19, 20)
 601007Leptin receptor1p31LEPR(21)
 601665Melanocortin 3 receptor20q13.2-q13.3MC3R(22, 23, 24)
 155541Melanocortin 4 receptor18q22MC4R(25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47)
 600456Neurotrophic tyrosine kinase receptor type 29q22.1NTRK2(12, 13)
 176830Proopiomelanocortin (adrenocorticotropin/β-ipotropin/α-melanocyte stimulating hormone/β-melanocyte stimulating hormone/β-endorphin)2p23.3POMC(48, 49)
 162150Proprotein convertase subtilisin/kexin type 15q15-q21PCSK1(50, 51)
 603128Single-minded homolog 1 (Drosophila)6q16.3-q21SIM1(52, 53)
Autosomal recessive    
 203800Alstrom syndrome2p13.1ALMS1(54, 55, 56, 57, 58, 59)
 209901Bardet-Biedl syndrome 111q13.1BBS1(60, 61, 62, 63, 64, 65, 66)
 606151Bardet-Biedl syndrome 216q13BBS2(61, 63, 67, 68, 69, 70)
 600151Bardet-Biedl syndrome 33p13-p12BBS3 (ARL6)(63, 71, 72, 73, 74, 75)
 600374Bardet-Biedl syndrome 415q22.3-q23BBS4(61, 76, 77, 78, 79, 80, 81)
 603650Bardet-Biedl syndrome 52q31BBS5(63, 82, 83, 84)
 604896Bardet-Biedl syndrome 620p12.2MKKS(63, 68, 71, 85, 86, 87, 88)
 607590Bardet-Biedl syndrome 74q27BBS7(67, 89)
 608132Bardet-Biedl syndrome 814q32.1BBS8(89, 90)
 269700Berardinelli-Seip congenital lipodystrophy 19q34.3AGPAT2(91, 92, 93, 94, 95)
 606158Berardinelli-Seip congenital lipodystrophy 211q13BSCL2(92, 94, 96, 97, 98)
 212065Carbohydrate-deficient glycoprotein syndrome type 1a16p13.2PMM2(99)
 216550Cohen syndrome8q22.2COH1(100, 101, 102, 103, 104, 105)
 601538Combined pituitary hormone deficiency5q35.3PROP1(106, 107, 108)
 227810Fanconi-Bickel syndrome3q26.31SLC2A2(109, 110, 111, 112, 113, 114, 115, 116, 117)
 139191Isolated growth hormone (GH) deficiency7p14GHRHR(118, 119, 120)
Triallelic digenic    
 138090Cortisone reductase deficiency1pter-p36.13H6PD(121)
 604931Cortisone reductase deficiency1q32-q41HSD11B1(121, 122)
Digenic    
 600917Severe insulin resistance with obesity3p25PPARG(123)
  7q31.1PPP1R3A 
Autosomal dominant    
 100800Achondroplasia4p16.3FGFR3(124, 125, 126, 127)
 103580AHO (Pseudopseudohypoparathyroidism)20q13.2-q13.3GNAS(128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147)
 103581AHO 215q11-q13AHO2(148)
 600430Brachydactyly mental retardation syndrome2q37.3STK25(149, 150, 151, 152, 153, 154, 155)
   GPC1 
   GPR35 
 105830Angelman syndrome with obesity15q11-q12ANCR(156)
 605746Anisomastia16q13-q21ANMA(157)
 160980Carney complex with primary pigmented nodular adrenocortical disease and Cushing's syndrome (CNC1)17q24.3PRKAR1A(158, 159, 160, 161, 162, 163, 164)
 605244Carney complex with primary pigmented nodular adrenocortical disease and Cushing's syndrome (CNC2)2p16 (165)
 604367Familial partial lipodystrophy, Dunnigan, type 33p25PPARG(166, 167, 168, 169)
 151660Familial partial lipodystrophy, type 2 (Dunnigan type)1q23.1LMNA(170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180)
 147670Insulin resistance syndromes19p13.3-p13.2INSR(181, 182, 183, 184, 185, 186, 187, 188)
 139250Isolated GH deficiency (139250)17q22-q24GH1(189)
 131100Multiple endocrine neoplasia, type 1 with Cushing's disease11q13MEN1 (Menin)(190, 191, 192, 193, 194, 195, 196)
 122000Posterior polymorphous corneal dystrophy (chromosome 1)1p34.3-p32.3COL8A2(197)
 605020Posterior polymorphous corneal dystrophy (chromosome 20)20p11.21VSX1(198, 199)
 176270Prader-Willi syndrome15q11.2IPW(200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 216, 217, 218, 220)
  15q11.2MKRN3 
  15q11.2PWCR1 
  15q12SNRPN 
  15q11.2MAGEL2 
  15q11.2NDN 
  15q11-q12GABRG3 
 603128Prader-Willi-like syndrome (chromosome 6q)6q16.3-q21SIM1(202, 213, 214, 215, 219, 220)
 190160Thyroid hormone resistance syndrome3p24.1THRB(221)
 181450Ulnar-Mammary (Schinzel) syndrome12q24.21TBX3(222, 223, 224, 225)
 194072WAGR syndrome with obesity11p13WT1(226, 227, 228, 229, 230, 231, 232)
  11p13PAX6 
X linked    
 301900Borjeson-Forssman-Lehmann syndromeXq26.3PHF6(233, 234, 235, 236, 237, 238, 239, 240)
 303110Choroideremia with deafness and obesityXq21.2CHM(241, 242)
  Xq21.1DFN3 
 309550Fragile X syndrome with Prader-Willi-like phenotypeXq28FMR1(243, 244, 245, 246)
 300148MEHMO syndromeXp22.13-p21.1MEHMO(247, 248, 249)
 300218Mental retardation X-linked, syndromic 7Xp11.3-q22.1MRXS7(250)
 300458Mental retardation X-linked, syndromic 16Xq28MECP2(251, 252)
 300238Mental retardation, X-linked, syndromic 11Xq26-q27MRXS11(253, 254)
 176270Prader-Willi-like syndrome, X-linkedXq23-q25PWLSX(255)
 312870Simpson-Golabi-Behmel 1Xq26.2GPC3(82, 256, 257, 258, 259, 260, 261, 262, 263, 264)
  Xq26.1GPC4 
 300209Simpson-Golabi-Behmel 2Xp22SGBS2(265)
 309585Wilson-Turner syndromeXq21.2-q22WTS(266, 267)

This year, there has been relatively nominal reporting of monogenic cases of obesity. The majority of the monogenic obesity cases remain those with a genetic defect (mutation, deletion, or insertion) in the melanocortin receptor 4 (MC4R) gene. Table 1 summarizes all of the cases that were reported in previous years. A publication by Farooqi and O'Rahilly (12) elegantly summarizes cases of monogenic obesity that received treatment for the mutated gene that resulted in improvement of the health status of the patients. These cases were covered in the 2004 Obesity Gene Map report. The same group recently described a new rare mutation in the receptor of the neurotrophin brain-derived neurotrophic factor (BDNF) gene, TrkB (13).

Neurotrophic Tyrosine Receptor Kinase 2 (NTRK2)

In humans, the receptor of the murine BDNF gene, TrkB, is encoded by the NTRK2 gene. A study was reported by Yeo and colleagues (13) whereby a de novo heterozygous mutation arose in a child with severe early-onset obesity and hyperphagia. The A-to-G transition resulted in amino acid substitution of the tyrosine residue at position 722 by a cysteine (Y722C) (Table 1). An additional cohort of 192 alleles and the proband's parents were screened for the presence of this rare mutation, but nobody was found to carry it. In vitro functional studies showed that the mutation impaired activation of MAPK when cells were treated with BDNF (13). This new rare mutation provides another example of single-gene mutations in genes involved in energy balance regulation that result in severe and early onset obesity. In another preliminary study of 288 individuals with a history of early onset obesity, five missense mutations were identified in NTRK2 (A74T, I98V, M354V, P660L, T821L) that have yet to be functionally characterized and described in greater detail (13).

Mendelian Disorders

Since last year's review, there has been limited development in the area of Mendelian disorders related to obesity, although many novel mutations in known genes have been reported. Updated references on new mutations for the Albright hereditary osteodystrophy (AHO), Bardet-Biedl, Berardinelli-Seip congenital lipodystrophy, Borjeson-Forssman-Lehmann, familial partial lipodystrophy, multiple endocrine neoplasia (type 1), and WAGR syndromes are provided (see Table 1).

In the present review, we now properly report AHO in the context of all disorders related to parathyroid hormone resistance, as described by DeSanctis et al. (131). To date, the AHO phenotype is always associated with mutations in GNAS1. In the AHO-like syndrome linked to 2q37, a French group narrowed down the critical region to a 4-megabasepair interval delimited by D2S2338 (present) and D2S2253 (deleted) (149).

A new mutation was discovered for familial partial lipodystrophy, Dunnigan type (167). The affected 21-year-old woman had a great excess of subcutaneous fat on the face, neck, trunk, and abdomen, with relative lack on the gluteal region, arms, and legs. She was insulin resistant and had the metabolic syndrome and type 2 diabetes. She was heterozygous for a novel A>G mutation at position −14 of intron B, upstream of PPARG exon 1 within the promoter of the PPARγ4 isoform, implicating this isoform as being potentially important in adipocyte biology.

Finally, in recent clinical reviews of large groups of Alstrom (58) and WAGR (229) syndrome patients, the central role of childhood obesity and hyperinsulinism in Alstrom syndrome was confirmed, as well as a significant prevalence of obesity (of 18%) in WAGR subjects. In this last syndrome, the new acronym WAGRO (obesity) has even been suggested (227).

Transgenics and KOs

The murine obesity gene map identifies 248 genes (Table 2) that, when mutated or expressed as transgenes in the mouse, result in phenotypes affecting body weight (BW) and adiposity. We include genes that promote obesity and genes that promote leanness, with the exception of genes that seem to promote failure-to-thrive phenotypes or mutant genes impacting developmental issues affecting multiple organs systems during embryogenesis or early growth. The list was compiled from the primary literature, accessible through PubMed and corroborated with information captured by the Mouse Genome Informatics (MGI) group (www.informatics.org). Official gene nomenclature rules have been followed, even where the use of this nomenclature differs from the gene name used in the primary publication. We have attempted to capture common synonyms, but the list is not exhaustive. Readers are directed to MGI for a more complete list of synonyms and nomenclature history.

Of the new genes added to the list this year, three are imprinted. Maternal inheritance of the Gnas KO allele (400), a KO of the paternally expressed Peg3 gene (493), and transgenic overexpression of the paternally expressed Mest (Peg1) in adipose tissue all promote obesity. Imprinted loci are well documented in the mouse genome, but the degree of imprinting can also be tissue dependent. Clearly, the role of imprinted genes in the development of obesity-related phenotypes must be considered in cases where simple Mendelian inheritance relationships seem uninformative. Three new genes listed for the first time this year are relevant to the molecular characterization of three well-known human obesity syndromes: Alstroms, Bardel-Biedl, and McKusick-Kaufman. The respective murine homologs, Alms1, Bbs2, and Mkks, all present obesity phenotypes when mutated in mice. Interestingly, Bbs2-deficient mice weigh less than controls at birth, suggesting an additional effect on early development. These three mutants will provide valuable model systems to study the roles of these genes in the development of these polygenic syndromes.

One particularly interesting addition to the gene list is the murine Clock gene. The CLOCK transcription factor is a key component of the molecular circadian clock within pacemaker neurons of the hypothalamic suprachiasmatic nucleus. Characterization of murine Clock mutants reveals an obesity phenotype that is accelerated during feeding with high-fat diet. Causative factors include an attenuated diurnal feeding rhythm, hyperphagia, and perturbation of the expression of hypothalamic peptides associated with the regulation of feeding behavior and energy balance. The effects of the CLOCK transcription factor seem to be associated with growth and development only after weaning because no differences in BW are observed in newborn pups or 3- or 4-week weaned mice.

Animal QTLs

The murine QTL information in Table 3 has been completely revised this year. Primarily, the names assigned to quantitative trait loci (QTLs) have been changed to conform to currently utilized nomenclature, and, in an attempt to more specifically define the location of the QTL on the mouse genome, we have included the genetic location of the peak logarithm of the odds ratio (LOD) score (or other statistical measure utilized) and a confidence interval (usually the 1 LOD interval). Information presented has been summarized from the primary literature and also from the MGI group at the Jackson Laboratory (www.informatics.jax.org). Clearly, the concept of QTL significance plays a large role in the identification of a QTL. We have attempted to adopt a uniform standard that identifies QTLs if they satisfy a genome-wide significance level below 0.05. QTLs that do not meet this are termed suggestive, and we have listed only suggestive QTLs that have either been corroborated in follow-up studies or replicated in another study using the same mouse strains. In cases of uncertainty, we have erred on the side of caution and listed the QTLs. For some recent studies, evidence for interactions between QTLs has been presented, despite no evidence of significance for the individual loci alone. Nomenclature rules may need to be revisited to describe these interactions. In the majority of the cases, QTL names listed in the table are not identical to those listed in the primary publication. In these cases, the names were changed by the MGI group to maintain conformity with existing nomenclature. Thus, names that have been listed in previous years may have been altered in this year's table.

Table 3.  QTLs reported for animal polygenic models of obesity
CrossQTLScoresVariance (%)PhenotypesAnimal chromosomeQTL peakReference
Cow       
 CGC × HerefordBTA17LWF = 8 −24 kg live weight17 (590)
Chicken       
 White Leghorn layer × commercial broilerBFc7 36-41F = 13.295.24Abdominal fat weight (9 weeks)7 (591)
 BFc7 36-41F = 11.504.51Abdominal fatness (9 weeks)7  
 BFc7 36-41F = 11.084.4Fat distribution (9 weeks)7  
 Rhode Island Red layer × Rhode Island Red layerBWc4 200-207p = 0.0125.8BW (40 weeks)4 (592)
 White Leghorn × Rhode Island RedGwchr4p = 0.0117Weight4 (593)
 Gwchr27p = 0.016Weight27  
 White Plymouth Rock × White Plymouth RockBw5F = 2.14 Weight (5 weeks)1 (594)
 Bw7F = 2.28 Weight (7 weeks)1  
 White Plymouth Rock × Rhode Island Red layerGfchr1LOD = 2.7518.1Fat (%), abdominal1 (595)
 Gwchr13LOD = 2.7726.6Weight13  
 Rhode Island Red layer × Rhode Island Red layerGAA01 263-287  Weight1 (596)
 GAA02 23-28  Weight2  
Mouse (multiple crosses)       
 (B6.129-Lipctm1Unc × SPRET/Ei)F1 × C57BL/6-Lipctm1UncBsbob  Body fat and adiposity281.7(456, 597)
 (B6.129-Lipctm1Unc × SPRET/Ei)F1 × C57BL/6JBsbob2  BW, fat mass, adiposity; interacts with Bsbob4 to regulate adiposity and BW762 (60 to 63.5) 
 (C57BL/6J × SPRET/Ei)F1 × C57BL/6JBsbob3  Interacts with Bsbob4 to regulate total cholesterol626.5 
 C57BL/6J/Lipc−/− × Mus spretus SPRET/EiBsbob4  Interacts with Bsbob3 to regulate total cholesterol; interacts with Bsbob5 to regulate body fat1252 
 Bsbob5  Interacts with Bsbob4 to regulate body fat1520.2 
  LOD = 3.626Interaction between Lipc (chromosome 9) and chromosome 7 locus7  
 (BALB/cJ × C57BL/6J)F1 × (C3H/HeJ × DBA/2J)F1D3Mit127p = 0.01 Leptin, 27%370.3(598)
 (C3H/He × Mus spretus)F1×Bw1LOD = 3.424BWX18 cM (DXMit57-DXMit48)(599)
  C57BL/6JBw2LOD = 6.6 BWXDXMit109-DXMit16 
 Bw3LOD = 4.3 BWX32 cM 
 Bw1  BWXDistal to DXNds1 
 Bw2  BWXDXMit60-DXMit16 
 Bw3  BWXDXMit3-DXMit12 
 (C57BL/6-Lipctm1Unc × SPRET/Ei)F1 × SPRET/EiBsbobLOD = 3.73Adiposity QTL present in BSBHLKO cross (BSB hepatic lipase-deficient animals) but not in BSB279 (75.6 to 81.1)(600)
 B6.S(D2mit194-D2Mit311)Bsbob  Confirmed to contain obesity QTL226.7- to 32.1-megabasepair interval 
 (C57BL/6J × SPRET/Pt)F1 × C57BL/6JHlbsb1LOD = 4.810.7Hepatic lipase activity764 (48 to 66)(601)
 Hlbsb2 7Hepatic lipase activity; interaction with Hlbsb13 to 7  
 (C57BL/6J × STRET/Ei)F1 × C57BL/6JMob1LOD = 4.66.5Fat (%)762(602, 603)
 Mob2LOD = 4.87.1Femoral fat63.05 
 Mob3LOD = 4.87Fat (%)1253 
 Mob4LOD = 3.45.9Mesenteric fat156.7 
 [High BW line (H) × low BW line (L)]F1 × high BW line (H)Bw19LOD = 13720Candidate gene Gpc3 identified in 660-kilobasepair intervalXDXMit226-DXMit68 (2 cM)(604, 605, 606)
 (Mus m. castaneus × C57BL/6J)F1 × M. m. castaneusPbwg1LOD = 3.1 to 10.910Stronger effect in females than males. Epistatic with Pbwg12 in males232.8 (26 to 44)(607, 608, 609)
 Pbwg2LOD = 3.13.9Male specific462 (39 to 86) 
 Pbwg3LOD = 2.6 to 3.63 772 (40 to 104) 
 Pbwg4LOD = 3.77.5Female specific; BW 5 weeks971 (46 to 96) 
 Pbwg5LOD = 3.43.7BW at 7 weeks1068 (42 to 94) 
 Pbwg6LOD = 4.95.2Stronger effect in males than females1353 (34 to 72) 
 Pbwg7LOD = 3.16.9Male specificX19 (0 to 48) 
 Pbwg8LOD = 412.1Male specific632 (14 to 50) 
 Pbwg9LOD = 3.84.5Stronger effect in females than males1014 (0 to 36) 
 Pbwg10p = 2.6 × 10−6 Interaction with Pbwg8 in malesX2.8 
 Pbwg12p = 9.1 × 10−6 Male specific and epistatic with Pbwg1 in males1234 
 Pbwg13p = 2.5 × 10−6 Interaction with Pbwg9 in females581 
 Pbwg14LOD = 2.8 BW at 8 weeks. Female specific51 (0 to 74) 
 Pbwg15LOD = 2.6 to 2.7 BW at 3 to 4 weeks943 
 Pbwg16LOD = 4.6 BW at 3 weeks1045 
 Pbwg17LOD = 4.2 to 4.9 BW at 6 to 10 weeks1346 
 Pbwg18LOD = 4.3 Female specific. Weight gain from 6 to 10 weeks1430 
 Pbwg19LOD = 3 Male specific. BW at 5 weeks162 
 Pbwg20LOD = 3.1 to 6.3 BW at 3 to 4 weeks190 (0 to 25) 
 Pbwg21LOD = 2.6 to 3.6 Male specific. BW at 3 weeks and weight gain 3 to 6 weeksX27 
 Pbwg22LOD = 2.9 to 4.3 Female specific. BW 9 to 10 weeksX35 
 C10bw2LOD = 3.6 Female specific917 
 C10bw3LOD = 3.4 Male specific1157 
 C10bw4LOD = 3.3 Female specific1346 
 C10bw6LOD = 4.3 Female specificX18.9 
 (Quackenbush-Swiss × C57BL/6J) × C57BL/6JNot assignedp = 0.00940BW and body length1056 to 65(610)
 129P3/J × C57BL/6JBwq5LOD = 4.44.8BW281.7(611)
 Bwq6LOD = 44.3BW961 
 Adip5LOD = 3.954.7Adiposity; interaction with Adip9926 
 Adip6LOD = 3.324.4Adiposity, interaction with Adip51663.2 
 129T2/SvEmsJ × EL/SuzObq1LOD = 812.3Adiposity728(612)
 Obq2LOD = 46.3Adiposity115 
 AKR/J × C57L/JObq3LOD = 5.17Adiposity253 (34 to 78.7 cM)(613)
 Obq4LOD = 4.66.1Adiposity174 (0 to 7) 
 AKR/J × SWR/JDob1LOD = 4.4 2004 = 4.8  450 (D4Mit5-D4Mit11)(614, 615)
 Dob2LOD = 4.8 Adiposity. QTL Not confirmed in (AKR × SWR) × SWR backcross mice960 (D9Mit11-D9Mit18) 
  2004 = 3.9     
 Dob3LOD = 3.9 Adiposity. QTL confirmed in (AKR × SWR) × SWR backcross1522.8 (D15Nds2-D15Mit22) 
 B6.V-Lepob/ob (leptin treated) × BALB/cJBwobLOD = 5  544(616)
 Mors1LOD = 5.6  1101.5 to 106.3 
 Mors2LOD = 3.4  352.5 to 71.8 
 Mors3LOD = 3.8 Testosterone1427.5 to 30 
 Mors4LOD = 3.4 Testosterone1415 to 27.5 
 B10.UW H3b we Pax1 un at/Sn X LOD = 4.61 Fat; adiposity adjusted for weight267.8 to 82(617)
 BALB/cA and TSOD × TSOD and BALC/cANidd5LOD = 5.91 BW and insulin234.5(618)
 Nidd6LOD = 4.65 BW177 
 BTBR.V-Lepob/ob × B6.V-Lepob/obMobe1LOD = 9.4814.110-Week body mass244 (41 to 47.1)(619)
 Mobe2LOD = 812.510-Week body mass1337 
 Mobe3LOD = 3.6 10-Week body mass565 
 Mobe4LOD = 2.49 10-Week body mass1734.4 
 C3H/He × NSYWaiting for identificationLOD = 6.8 BMI635.5 (32 to 60)(620)
 C57BL/6-insrtm1Dac/+, irs1tm1Jos/+ × 129S6/SvEvTacE1ptLOD = 3.733Leptin. Interacts with hyperinsulinemia QTL, Hypn750(621)
 C57BL/6J × 129S1/SvImJObq16LOD = 10 Females848 (42 to 53)(622)
 Obq17LOD = 2.3 Females174 (48 to 108) 
 Obq18LOD = 2.9 Interacts with Obq16 (females)965 (0 to 75) 
 Obq19  BMI (females)178 (38 to 72) 
 Mob2LOD = 2.6 (Females)60 (0 to 10) 
 C57BL/6J × 129S6/SvEvTacD3Mit127LOD = 2.778 370.3(623)
 D10Mit162LOD = 2.928 1059 
 D12Mit231LOD = 3.225 1248 
 D14Mit192LOD = 352 1440 
 C57BL/6J × A/JBw8q1LOD = 4.42BW, 8 weeks1100 (77 to 102)(624)
 Bw8q2LOD = 3.34BW, 8 weeks466 
 C57BL/6J × B6.AChr16DiobqLOD = 4.3 Chromosome substitution strain1653.8 (29 to 55.2)(625)
 C57BL/6J × CAST/EiMob5LOD = 5.8 Subcutaneous fat295.5 (75 to 109)(626, 627)
 Mob6LOD = 7.3 Subcutaneous fat. QTL confirmed in B6.CAST (73 to 83 cM) congenic mice249.6 (35 to 85) 
 Mob7LOD = 5.8 Retroperitoneal and subcutaneous fat2Peak at D2Mit9 37 (30 to 46) 
 Mob8LOD = 4.7 Body fat (%)9D9Mit8 
 Not assignedLOD = 5.2 Leptin level (no obesity)4  
 Bdln2LOD = 4.3 Body length1515 
 C57BL/6J × CAST/EiJMnif1LOD = 87.1Fat, intake822 (10 to 30)(628)
 Mnif2LOD = 65.4Fat, intake1824 (10 to 58) 
 Mnif3LOD = 43.6Fat, intakeX18 (10 to 58) 
 Mnic1LOD = 6.76Carbohydrate intake1710 (3 to 24) 
 Mnic2LOD = 3.43.1Carbohydrate intake646 (36 to 64) 
 Mnic3LOD = 4.13.7Carbohydrate intakeX40 (14 to 61) 
 Kcal1LOD = 7.76.8Kilocalorie intake1820 (10 to 26) 
 Kcal2LOD = 4.94.4Kilocalorie intake1716 (8 to 37) 
 C57BL/6J × DBA/2JNot assignedLOD = 3.336-Week weight176 (46 to 84)(629, 630)
 Not assignedLOD = 3.346-Week weight426 (24 to 30) 
 Not assignedLOD = 3.246-Week weight560 (57 to 64) 
 Not assignedLOD = 4.356-Week weight535 (22 to 45) 
 Not assignedLOD = 446-Week weight622 (15 to 26) 
 Not assignedLOD = 3.346-Week weight426 (24 to 30) 
 Not assignedLOD = 6.996-Week weight725 (23 to 33) 
 Not assignedLOD = 4.456-Week weight932 (12 to 50) 
 Not assignedLOD = 5.766-Week weight1145 (29 to 49) 
 Not assignedLOD = 4.146-Week weight1359 (29 telomere) 
 Not assignedLOD = 336-Week weight140 (0 to 22) 
 Not assignedLOD = 4.976-week weight1714 (11 to 18) 
 Pfat1LOD = 520Predicted fat (%)430 
 Pfat2LOD = 4.920Predicted fat (%)631.8 
 Pfat3LOD = 5.320Predicted fat (%)1320 
 Pfat4LOD = 8.620Predicted fat (%)1543.3 
 C57BL/6J × KK-AyBwq1LOD = 5.515BW at 50 days of age421.9 (6.3 to 32)(631, 632)
 Bwq2LOD = 8.826BW from 40 to 100 days of age; modifier of Ay635.2 (29 to 47) 
 C57BL/6J × KK/H1LtObq5LOD = 717Adiposity (females)919(633)
 Obq6LOD = 515.7Adiposity (males); except mesentericX16 
 UnassignedLOD = 4.4 (6.9)  7  
 UnassignedLOD = 5.9  9  
 UnassignedLOD = 4.2  7  
 C57BL/6J × NZB/B1NJBwefmLOD = 5.11  570(634)
 Bwem1LOD = 3.16  554 
 Bwem2LOD = 4.53  1335 
 C57BL/6J-Socs2hg/hg × CAST/EiCarfhg1LOD = 2.56.2Fat content538(635)
 Carfhg2LOD = 5.812.5Fat content9  
 wg1  2 to 9 weeks231 
 wg2 10.42 to 9 weeks261 
 wg3  2 to 9 weeks845 
 wg4  2 to 9 weeks1146 
 C57BL/6J-Socs2hg/hg × CAST/EiMohg1p = 0.004  246 to 50.3(636)
 Mohg2p = 0.021  X3 
 Mohg 3p = 0.041  X37 
 C57BLKS/J-Cpefat × HRShr/+Fina1LOD = 6.8413Adiposity index1140 (30 to 50)(637)
 Bwt1LOD = 14.0324Interaction with locus on chromosome 18 (47 cM)1422.5 (20 to 35) 
 CAST/Ei × C57BL/6JDob4LOD = 3.1 to 4.314Fat, mesenteric418.35(638)
 CFLP (P6) × JU/CBABw19LOD = 24.417 to 2010-Week weightX24.64(639)
 Du6 × DuKImebt2  BW1425 (19 to 32)(640)
 DU6i × DBA/2JBw4F = 9.524.9 1155 (36 to 65)(641, 642)
 Bw5F = 10.445.4BW136 (11 to 97) 
 Bw7F = 5.342.8 459 (34 to 72) 
 Bw9F = 3.872.1 1217 (0 to 50) 
 Bw10F = 6.393.4 1347 (33 to 61) 
 Bw13F = 11.76BW581 (73 to 89) 
 Bw14F = 25.912.3BW728 (23 to 33) 
 Bw15F = 7.363.8BW1310 (3 to 16) 
 Bw16F = 7.523.9BW1114 (6 to 17) 
 Afpq1F = 6.173.2 329 (23 to 37) 
 Afpq2F = 5.723 466 (60 to 72) 
 Afpq4F = 4.252.3 1313 (0 to 46) 
 Afpq5F = 5.863.1 119 (0 to 19) 
 Afpq6F = 8.924.6Abdominal fat (%)1736 (27 to 51) 
 Afpq9F = 18.59.1Abdominal fat (%)722 (13 to 27) 
 Afpq10F = 7.483.9Abdominal fat (%)1218 (10 to 26) 
 Afw1F = 4.232.3 330 (23 to 36) 
 Afw2F = 5.723 466 (60 to 72) 
 Afw3F = 5.673 580 (69 to 91) 
 Afw5F = 6.483.4 1112 (2 to 19) 
 Afw6F = 6.033.2 1311 (4 to 18) 
 Afw7F = 94.7 1739 (30 to 52) 
 Afw9F = 24.912Abdominal fat (%)723 (16 to 28) 
 Afw10F = 8.564.5Abdominal fat (%)1221 (15 to 27) 
 Afw11F = 4.782.5 X17 (0 to 39) 
 Lepq1F = 7.584.4Leptin1428 (21 to 41) 
 Abfp1  Interacts with Abfp2 and Abfp31734 
 Abfp2  Interacts with Abfp11158 
 Abfp3  Interacts with Abfp1816 
 Abfp4  Interacts with Abfp5326 
 Abfp5  Interacts with Abfp4520 
 Abfw1  Interacts with Abfw2, Abfw3, Abfw41160 
 Abfw2  Interacts with Abfw1464 
 Abfw3  Interacts with Abfw11732 
 Abfw4  Interacts with Abfw11943 
 Abfw5  Interacts with Afbw6572 
 Abfw6  Interacts with Afbw5126 
 Bodw1  Interacts with Bodw2218 
 Bodw2  Interacts with Bodw11155 
 Bodw3  Interacts with Bodw415 
 Bodw4  Interacts with Bodw3934 
 DuK × Du6Afw1F = 4.524Abdominal fat weight351(643)
 Bw4F = 4.7923.1BW1142 (36 to 50) 
 Afw2F = 4.8913.4Abdominal fat451 (34 to 63) 
 Afpq2F = 4.8910.2Abdominal fat455 (31 to 79) 
 Afw5F = 4.798.3Abdominal fat116 (0 to 29) 
 Afpq4F = 4.75.3Abdominal fat130 
 Afpq1F = 4.528.3Abdominal fat (%)346 (24 to 76) 
 Afpq3F = 4.134.7 551 
 Afw3F = 4.133.9 561 
 Afw4F = 5.134.1 929 
 Afw6F = 4.77.7 130 (0 to 10) 
 Afw7F = 4.212.9 1746 
 Afw8F = 3.6818.1 1926 
 Bw5F = 4.617.1 114 
 Bw6F = 5.025.1 256 
 Bw7F = 4.897 455 
 Bw8F = 4.133 542 
 Bw9F = 3.84.3 1249 
 Bw10F = 4.710.1 1334 
 Bw11F = 4.724.2 156 
 Bw12F = 3.730.2 X42 
 F × LFob1LOD > 3.34.914-week fat (%)245(644)
 Fob2LOD = 3.319.514-week fat (%) (in females)1219 
 Fob3LOD = 11.314.414-week fat (%)1534 
 Fob4LOD = 3.37.314-week fat (%)X37 
 F × LFob3LOD = 11.314.4 15(12 to 78)(645, 646)
 Fob3a  Subcongenics of Fob31527 (22 to 32) 
 Fob3b  Subcongenics of Fob3; positional and expression candidate is Sqle (squalene epoxidase)1568 (44 to 72) 
 F.L. congenicFob3aF = 13.71.6Fat (%); late-onset15 (645)
 Fob3bF = 11.60.7Fat (%); early onset15  
 ICR × M16Mfiq5LOD = 3.41.8 157 (34 to 103)(647)
 Mfe5q1LOD = 3.72.3 854 (1 to 81) 
 Mfiq3LOD = 3.72 97 (7 to 60) 
 Mfi5q1LOD = 4.42.3 960 (7 to 60) 
 Mfi7q1LOD = 5.32.4 1129 (15 to 74) 
 Mfi8q1LOD = 4.82.2 1132 (22 to 86) 
 Mfiq1LOD = 8.14.7 1134 (22 to 68) 
 Mfe5q2LOD = 3.62.2 1140 (18 to 73) 
 Mfeq1LOD = 4.93 1150 (18 to 73) 
 Mfiq4LOD = 3.72 1235 (17 to 63) 
 Mfiq2LOD = 4.42.4 1354 (26 to 54) 
 Mlepq1LOD = 7.75.7 293 (83 to 104) 
 Mlepq2LOD = 3.42.3 1752 (15 to 68) 
 Not assignedLOD = 16.87 284 (82 to 92) 
 Not assignedLOD = 41.2 822 (1 to 82) 
 Not assignedLOD = 5.21.8 1151 (36 to 65) 
 Not assignedLOD = 4.32 1752 (22 to 58) 
 Not assignedLOD = 12.14.8 283 (80 to 89) 
 Not assignedLOD = 4.61.8 441 (2 to 62) 
 Not assignedLOD = 3.61.5 1158 (41 to 75) 
 Not assignedLOD = 5.12 1738 (18 to 57) 
 Not assignedLOD = 14.26.5 285 (83 to 93) 
 Not assignedLOD = 5.11.9 728 (8 to 51) 
 Not assignedLOD = 62.6 1158 (32 to 64) 
 Not assignedLOD = 3.31.9 1751 (14 to 63) 
 ILS inbred, long sleep) × ISS (inbred short sleep)Wght1LOD = 4.6 Interacts with Wght2178(648)
 Wght2LOD = 4.5 Interacts with Wght143.2 
 Wght3LOD = 8.6  452.6 
 Wght4LOD = 3.22  573 
 Wght5LOD = 7.6  1175 
 Wght6LOD = 9.4  1920 
 KK/Ta × (BALB/c × KK/Ta)F1Tgls1LOD = 2.1 Triglyceride and BW459(649, 650)
 D17Mit218LOD = 2.9 BW1742 
 Azgp1LOD = 2.3 BW candidate gene578 
 LG/J × SM/JAdip1LOD = 2.4 Adiposity (males)111(620, 651, 652, 653, 654)
 Wta1LOD = 2.35 Late weight gain46.5 
 Wta2LOD = 3.49 Late weight gain667 
 Adip2LOD = 3.71 Adiposity/weight (females)646.3 
 Adip3LOD = 3.71 Adiposity (males)/weight746.4 
 Adip4LOD = 2.57 Adiposity832 
 Adip5LOD = 1.84 Adiposity942 
 Adip6LOD = 2.69 Adiposity (males)1245 
 Adip7LOD = 1.9 Adiposity (males)131 (0 to 30) 
 Wta3LOD = 2.7 Weight142.5 
 Wta4LOD = 2.44  1717.4 
 Adip8LOD = 2.84 Adiposity1820 (8 to 38) 
 LG/J × SM/JNot assigned   7 (654)
 Not assignedLOD = 3.7  766 (65.6 to 69) 
 Not assignedLOD = 4.07  1722.8 (17.7 to 24.2) 
 Not assignedLOD = 3.68 Also epididymal, retroperitoneal, and mesenteric162 (56.6 to 65) 
 Not assignedLOD = 3.21rAlso retroperitoneal, mesenteric, and leptin859 (32 to 59) 
 Not assignedLOD = 3.58rAlso Retroperitoneal & mesenteric1063 (59 to 70) 
 Not assignedLOD = 3.5 Also mesenteric and leptinX69 
 Not assignedLOD = 4.99  1110.9 (1.1 to 17) 
 M16i (rapid 3- to 6-week weight gain) × L6 (low 6-week weight)Scfq1LOD = 7.65.9Fat, subcutaneous284 (81.7 to 88.9)(655, 656, 657, 658)
 Scfq2LOD = 4.45Fat, subcutaneous1525.2 (8.8 to 39.6) 
 Scfq3LOD = 4.13.8Fat, subcutaneous1124.9 (9.9 to 47.5) 
 Scfq4LOD = 4.13.4Fat, subcutaneous1721.9 (0 to 34) 
 Scfpq1LOD = 3.912Fat, subcutaneous, adjusted for 10-week weight1033.1 (20.5 to 55.3) 
 Epfpq1LOD = 65.3 1420.3 (0 to 34.5) 
 Epfpq2LOD = 3.81 266.8 (52.2 to 72.7) 
 Epfpq3LOD = 3.63.3 1551.1 (46.3-ter) 
 Epfpq4LOD = 3.43.4 1533.4 (21.2 to 46.3) 
 Epfq1LOD = 9.56.7 284 (79.8 to 87.6) 
 Epfq2LOD = 4.64.3 297.6 (95.5 to 102.4) 
 Epfq3LOD = 3.83 1721.9 (0 to 33.2) 
 Epfq4LOD = 3.52.5 1117.4 (0 to 34.9) 
 Epfq5LOD = 3.42.6 721.5 (0 to 35.9) 
 W10q1LOD = 299.4 279.6 (76.8 to 81.7) 
 W10q10LOD = 8.34.8 455.3 (41.1 to 61.8) 
 W10q11LOD = 7.98 628.5 (20 to 47.2) 
 W10q12LOD = 6.92.1 1719.2 
 W10q13LOD = 5.77 953.9 (44.5 to 61.4) 
 W10q14LOD = 5.2  826.4 (19.2 to 41.4) 
 W10q15LOD = 4.83.1 1730.9 (24.5 to 41.1) 
 W10q16 2.8 542.8 (29.4 to 61.8) 
 W10q17LOD = 4.21 1355.4 
 W10w18LOD = 4.11.9 718.2 
 W10q2LOD = 26.48.1 1117.7 (11.3 to 24.1) 
 W10q3LOD = 15.57 329.7 (23.7 to 40.5) 
 W10q4LOD = 14.99.5 347.7 (40.5 to 54) 
 W10q5LOD = 10.25.3 1031.7 (24.8 to 42.6) 
 W10q6LOD = 9.73.9 156.3 (48.7 to 66.5) 
 W10q7LOD = 9.13 172.6 (66.5 to 79) 
 W10q8LOD = 10.25.3 1031.7 (24.8 to 42.6) 
 W10q9LOD = 8.68.6 250.8 (42.4 to 63.3) 
 MH × C57BL/6JHlq1LOD = 5.64.7Heat loss; confirmed in (MH × ML)F2 cross1127(659)
 Hlq2LOD = 3.73.1Heat loss271 
 Hlq3LOD = 3.83.1Heat loss335 
 Hlq4LOD = 4.73.9Heat loss33.9 
 Hlq5LOD = 4.13.4Heat loss761 
 Fatq1LOD = 7.4 to 8.05.4 to 5.9Gonadal fat162 
 Batq1LOD = 3.963.3Brown fat1102 
 Batq2LOD = 3.462.8Brown fat355 
 Wt10q1LOD = 4.253.3 125 
 Wt10q2LOD = 4.763.8 361 
 Wt10q3LOD = 3.632.9 1132 
 Wt3q1LOD = 5.134.1 172 
 Wt3q2LOD = 10.098 1108 
 Wt3q3LOD = 6.285 1714 
 Wt6q1LOD = 4.023.3Confirmed in (MH × ML)F2 cross127 
 Wt6q2LOD = 3.983.2 1108 
 Wt6q3LOD = 4.553.7 1136 
 Mhi (inbred, high food intake) × Lhi (inbred, low food intake)Not assignedF = 10.474.9 573 (66-telomere)(660)
 Not assignedF = 10.484.7 749 (35 to 68) 
 Not assignedF = 34.2814.4*Non-Mendelian87 (1 to 19) 
 Not assignedF = 7.983.6 947 
 Not assignedF = 7.023.2 1840 
 NON/Lt × (NZO/H1Lt × NON/Lt)F1Dbsty1LOD = 9.36 BW121 (8.3 to 43.1)(661)
 Dbsty2LOD = 3.86 Adiposity index543 
 Dbsty3LOD = 4.88 Adiposity index1248 (45 to 53) 
 NZM/B1NJ × SM/JBfq1LOD = 3.636Body fat281(662)
 NZO × (SJL/x NZO)F1Nobq1LOD = 3.816.8BMI (females)532(663, 664, 665)
 SM/J × A/JBwq3LOD = 4.66BW at 10 weeks856 (53 to 69)(666)
 Bwq4LOD = 4.86BW at 10 weeks1828 (20 to 54) 
 SM/J × NZO/H1LtObq4LOD = 6.3 Inguinal fat (%) (males)178.7 (6.1 to 15.5)(667)
 Obq7LOD = 6 Mesenteric fat (%) (males)128.7 (25.7 to 42) 
 Obq8LOD = 6.4 Retroperitoneal fat (%)161.9 (63.7 to 85.1) 
 Obq9LOD = 6.7 Mesenteric fat (%) (females)188.4 (82.4 to 92.7) 
 Obq10LOD = 6.4 Gonadal fat (%) (males)258.1 (50.7 to 67.4) 
 Obq11LOD = 4.1 Gonadal fat (%)510 (3.4 to 16.9) 
 Obq12LOD = 4.5 Gonadal fat (%)529 (21.9 to 36.1) 
 Obq13LOD = 9.3 Mesenteric fat (%)626.8 (20.7 to 29.4) 
 Obq14LOD = 9.2 Mesenteric fat (%)643.5 (39.4 to 46.9) 
 Obq15LOD = 6.6 Gonadal fat (%) (males)751.4 (44.2 to 52.4) 
 (C57BL/6J × TH)F1 × TH and (CAST/Ei × TH)F1 × TH (TallyHo) × variousTabw Tafat Tabw2LOD = 3.9 LOD = 3.1  7 4 627.8 (0 to 44) 69.8 (68 to 90) 38.5 (19.1 to 65.5)(668, 669)
Sheep       
 Texel × TexelGDF8p < 0.0019.9% Less fatFat  (670)
Rat       
 (OLETF × BN) × OLETFDmo9LOD = 3.5 Adiposity index11 (671)
 Dmo1LOD = 8.2 to 14 BW1  
 Dmo4LOD = 4.4 to 5.5 Adiposity index1  
 Dmo7pLOD = 4.9 to 5.4 Adiposity index7  
 Dmo6pLOD = 3.5 to 3.6 Adiposity index6  
 Dmo5LOD = 3.5 to 3.6 Adiposity index3  
 Dmo10LOD = 3.5 to 3.6 BW11  
 BN × GK/Nidd/gk5Nidd/gk5 weightLOD = 4.1913Weight8 (672)
 Dahl × MNSDAHL3p = 0.0000313BW3 (673)
 F344 × OLETFOlep1LOD = 5.396.5Leptin2 (674)
 Olep2LOD = 4.498Leptin6  
 GK × BNNidd/gk6  BW17 (675)
 Nidd/gk1  Adiposity1  
 bw/gk1  BW7  
 Nidd/gk5  BW8  
 GK × F344Niddm1LOD = 3.223.5BW1 (676)
 Weight1LOD = 6.2  7  
 Niddm3LOD = 3.0  10  
 Lepr(fa)/Lepr(fa) 13M × WKYQfa12LOD = 38.3BMI, female12 (677)
 Qfa1LOD = 2.26.9BMI, female1  
 OLETF × BNDmo1LOD = 611.6BW1 (678)
 OLETF × F344Niddm24LOD = 3.91 Also known as Nidd6/of1 DistalD1Rat81-D1Rat90(679)
 Obs5LOD = 5.1 Obs5 narrowed to 10-cM interval14D14Rat23-D14Wox7(680)
 SHR × BB/OKSHR4LOD = 3.114BW (females)4 (681)
 SHR1LOD = 3.332BW (males)1  
 SHR × wildSHR10LOD = 3.5 BW (males)10 (682)
 WOKW × DA/KWokw1/Q1ms5LOD = 4.516BMI5 (644, 683)
 Wokw1/Q1ms1LOD = 4.93130-Week BW1  
Pig       
 Berkshire × YorkshireSSC4:113F = 11.86Weight4 (684)
 SSC7F = 13.86.9Back fat7  
 SSC1F = 11.34.8Back fat1  
 SSC5F = 9.54.8Back fat5  
 Duroc × BerkshireSSC2 0F = 10.03 Back fat2 (685)
 SSC2 30F = 10.61 Fat (%)2  
 SSC2 37F = 7.34 Weight2  
 SSC6 110F = 7.39 Weight6  
 Duroc, Hampshire, Landrace × MeishanPigQTL2F = 7.9 Average back fat7 (686, 687)
 Duroc, Hampshire, Landrace × MeishanHMGA1p = 0.01 Back fat7 (669)
 Large White × European wild boarFAT1p = 0.00019.7Body fat (%)4 (688, 689, 690)
 Landrace × IberianFAT1F = 11.1 Back fat depth4 (691)
 Landrace × IberianFAT1  Weight  (692)
 Landrace × IberianSSC6 60-100p = 0.001 Back fat thickness6 (693)
 SSC6 130-132/LEPRp = 0.001 Back fat thickness, intramuscular fat (%)6  
 Landrace × IberianAFABP  Fatness4 (692)
 Meishan × (Dutch Landrace × Large White)SSC7F = 18 Back fat thickness7 (694, 695)
 Meishan × (Dutch Landrace × Large WhiteSSC2F = 2.7 Back fat thickness2 (694, 695)
 Meishan × DurocSSC6 102, 7-116.7F = 16.164Weight6 (696)
 SSC6 102, 7-116.7F = 12.6514Weight, daily gain6  
 SSC7 56.2F = 11.4512Weight, daily gain7  
 SSC7 113.3F = 13.614Fat, back fat thickness7  
 SSCX 74, 6F = 15.7916Fat, intramuscularX  
 Meishan × DurocHMGA2p = 0.0114Fat, back fat thickness7 (669)
 Dutch × MeishanSSC6qF = 14.70.1 to 0.2Intramuscular fat6q (465, 697)
 SSC7F = 49.4 Back fat thickness7  
 SSC2F = 24.1 Back fat thickness2  
 SSC6pF = 14.5 Intramuscular fat6p  
 SSCXF = 12.80.1 to 0.2Intramuscular fatX  
 Gottingen × MeishanSSC7F = 19.518Back fat thickness7 (698)
 Large White × MeishanBFM4  Midback fat depth4 (699)
 Meishan × Large WhiteSSCX 67p = 1.4e15 Fat thickness at the loinX (700)
 White × MeishanSSC4:49-84F = 14.9 to 15.33 to 4Back fat thickness4 (701, 702)
 SSC8F = 9.51 to 2Back fat thickness8  
 SSC7F = 10.4 to 20.52 to 5Back fat depth7  
 SSC1F = 39.4 to 94.91 to 2Weight1  
 SSC5F = 13.4 to 15.12 to 5Back fat thickness5  
 SSC6F = 11.91 to 2Back fat thickness6  
 SSCXF = 37.4 to 71.8 Back fat depthX  
 White composite × MeishanSSC7F = 14.7 Back fat thickness7 (703)
 SSC1F = 15.4 Back fat thickness1  
 SSCXF = 32.3 Back fat thicknessX  
 Hampshire, Landrace × MinghuPIT1F = 3.34 42-Day weight13 (704)
Large White × Wild BoarIGF2qF = 7.110.4Back fat depth2p (634, 705)

QTLs may be identified from several different types of genetic crosses. We have listed this information in this year's table. Typically, F2 intercrosses or backcrosses are utilized. However, there is likely to be an increasing use of recombinant inbred strains, advanced intercross lines, and congenic strains (that contain a specific donor genetic segment on a different background strain). It must be remembered that QTLs identified from phenotyping and genotyping of crosses between two strains define only a statistical probability of a polymorphic gene residing in a defined genetic interval. Follow-up studies are necessary to confirm this likelihood. Congenic (and subcongenic) strains have been generated for some of these QTLs, supporting the existence and magnitude of some of these phenotypes. Some cases include the characterization of the Fob3 QTL (645, 646). Congenic strains containing a chromosome 15 region from the lean L strain were introgressed onto the F genetic background. Interestingly the characterization of subcongenic lines suggests that Fob3 contains two contributory regions: Fob3a and Fob3b, conferring late and early onset phenotypes, respectively. Expression analysis of genes positioned within the Fob3b segment by microarray screening identifies a candidate gene, Sqle (squalene epoxidase). This gene is involved in the regulation of cholesterol biosynthesis. Interestingly, the expression of other genes of the cholesterol biosynthesis pathway mapping outside of the Fob3b region are also perturbed, suggesting that the changes in activity of this pathway may be responsible for the phenotypic differences between the F parental and the F.L<Chr15> congenic strains. Other murine QTL regions for which candidate genes have been implicated include Bw19 (Gpc3, Glypican 3) (606) and the QTL on chromosome 7 associated with adiposity (ATP10a, encodes ATPase, class V, type 10A) (706). A candidate gene for a rat QTL Niddm24 is Pnlip (encodes pancreatic lipase). The continued generation of congenic mouse strains and expression screening and single nucleotide polymorphism genotyping analysis should continue to implicate specific genes with well-characterized QTL regions.

QTLs from Cross-Breeding Experiments Other Than Rodents

Syntenic regions in humans have been picked up directly from the original papers or determined from the U.S. Livestock Genome Mapping Projects (NAGRP03). Four new chromosomes were targeted according to QTL analysis in chicken, one in pig, and one in sheep (Table 3). In a cross between Landrace and Iberian pig strains, a QTL for fatness was reported on pig chromosome 4 in the region of the AFABP gene (692) corresponding to the human fatty acid-binding protein 4 (adipocyte) gene located at 8q24. A QTL for fat was reported in a sheep Texel × Texel cross at the growth differentiation factor 8 gene (670), which is located at 2q32.2 in humans. The main QTL region detected for fat on chicken chromosome 7 from the cross White Leghorn layer × commercial broiler (591) corresponded to human chromosome 2q21. The cross of Rhode Island Red layer with itself produced a QTL for BW on chromosome 4 (707) corresponding to human chromosome 17q11.1-q12, whereas the White Plymouth Rock cross produced a QTL for weight on chromosome 5 (594) corresponding to human 22q13.1-q13.31 but also to 12p13-q23 reported in the cross WL × RIR (593). Finally, a QTL for weight was reported on chicken chromosome 1 (596) that corresponds to human chromosome 21q22.

Associations with Candidate Genes

The evidence for associations between candidate genes and obesity-related phenotypes is summarized in Table 4. A total of 416 studies covering 127 candidate genes have reported significant associations. Of these, 57 studies (40 candidate genes) were published during the past year. This year's update includes 14 new candidate gene entries.

Table 4.  Evidence for association between markers of candidate genes with obesity-related phenotypes
GeneLocationSubjectsPhenotypepReference
ABCC811p15.1232 CasesObesity, morbid0.02(708)
ABCG52p21262 CasesBMI0.05(709)
ACE17q24.11009 MenBMI0.012(710)
  964 MenWaist circumference0.0023(710)
  956 SubjectsOverweight (Blacks from U.S.)0.03(711)
  1059 SubjectsOverweight (Blacks from Nigeria)0.04(711)
  956 SubjectsObesity (Blacks from U.S.)0.02(711)
  1059 SubjectsObesity (Blacks from Nigeria)0.04(711)
  922 SubjectsBody fat (%) (physically active Health ABC subjects)0.05(712)
  959 CasesOverweight0.014(713)
  186 CasesBMI0.04(714)
ACP12p2575 CasesBMI (in children)0.02(715)
  265 CasesBMI (in type 2 diabetic subjects)0.002(716)
ADA20q13.12273 CasesBMI (in type 2 diabetic subjects)0.0004(717)
ADIPOQ3q27194 SubjectsBMI0.017(718)
  811 Subjects, 45 familiesBMI (Hispanic families from IRAS)0.004(719)
  811 Subjects, 45 familiesWaist circumference (Hispanic families from IRAS)0.001(719)
  811 Subjects, 45 familiesAbdominal visceral fat (Hispanic families from IRAS)0.01(719)
  100 Subjects, 100 womenBMI (women with polycystic ovarian syndrome)0.01(720)
  770 SubjectsWeight change during acarbose trial (STOP-NIDDM trial cohort)0.043(721)
  4479 Cases3-year increase in BMI0.033(722)
  4479 Cases3-year increase in waist-to-hip ratio0.01(722)
  103 CasesBMI0.03(723)
  995 CasesObesity0.047(724)
  413 CasesBody weight, waist circumference (in Japanese, in whites)0.03(725)
  371 CasesBMI0.02(726)
  95 CasesBMI (in obese women)0.014(727)
  95 CasesSagittal abdominal diameter (in obese women)0.032(727)
  245 CasesBMI0.05(728)
ADRA2A10q24-q26213 CasesSkinfolds, trunk-to-extremity ratio (in Blacks)0.04(729)
  72 CasesSkinfolds, trunk-to-extremity ratio (in women)0.002(730)
  476 CasesAbdominal total fat0.003(731)
  476 CasesAbdominal subcutaneous fat0.012(731)
  93 Cases, 49 men, 44 womenWeight change (Chinese schizophrenic under anti-psychotic)0.023(732)
ADRA2B2q11.2166 CasesBasal metabolic rate (in obese non-diabetics)0.01(733)
  126 CasesBody weight, change, 5-year (in non-diabetics)0.04(734)
ADRB110q24-q26931 CasesBMI, body weight, fat mass0.05(735)
  760 SubjectsBMI increase during 15-year follow-up0.018(736)
ADRB25q31-q32239 CasesWaist-to-hip ratio0.05(737)
  180 CasesBMI0.003(738)
  494 CasesBody weight, increase (in men)0.01(739)
  141 CasesCatecholamine-induced lipolysis in adipocytes0.01(740)
  247 CasesBMI, change (in women)0.04(741)
  247 CasesFat mass, change (in women)0.0008(741)
  247 CasesBody fat (%) change (in women)0.0003(741)
  230 CasesSkinfolds, sum of eight (in men)0.03(741)
  236 CasesLipolysis0.02(742)
  508 CasesBMI (in Japanese)0.001(743)
  272 SubjectsBMI (African Americans from IRAS)0.001( 7)(44)
  992 SubjectsBMI (whole IRAS cohort)0.045(744)
  992 SubjectsWaist-to-hip ratio (whole IRAS cohort)0.0001(744)
  948 SubjectsAbdominal visceral fat (whole IRAS cohort)0.0001(744)
  140 CasesBMI, fat mass, fat cell volume0.001(745)
  826 CasesBMI, obesity, waist-to-hip ratio, waist circumference, hip circumference0.05(746)
  366 CasesBMI (in women)0.01(747)
  836 CasesBMI, body weight, waist-to-hip ratio, waist circumference, hip circumference (in French men)0.002(748)
  63 CasesBMI, fat mass0.05(749)
  277 CasesBMI (in Japanese men)0.004(750)
  1576 CasesBMI0.02(751)
  284 CasesLeptin0.03(752)
  224 CasesBMI (in men)0.01(731)
  24 CasesLeptin, body weight, increase, skinfolds, sum of eight0.03(753)
  286 CasesBody weight, increase0.04(754)
  574 CasesBMI (in Japanese)0.009(755)
ADRB38p12-p11.2185 CasesBody weight, increase over 20 years, weight, current0.007(756)
  313 CasesObesity (in those 20 to 35 years old)0.05(757)
  476 CasesBMI (in men)0.05(758)
  553 CasesObesity (in Japanese children)0.02(759)
  179 CasesBMI0.006(760)
  295 CasesBMI0.05(761)
  695 CasesBMI0.001(762)
  83 CasesBMI (in coronary artery disease patients)0.05(763)
  211 CasesObesity, moderate0.02(764)
  53 CasesObesity0.05(765)
  350 CasesBMI0.009(766)
  398 CasesBMI, abdominal subcutaneous fat, abdominal visceral fat0.02(767)
  154 CasesObesity (in sedentary individuals)0.05(768)
  46 Cases5-year weight gain0.05(769)
  586 CasesBMI, hip circumference (in women)0.03(770)
  56 CasesBMI, fat mass, waist circumference0.05(771)
  128 CasesBody weight, increase over 25 years0.01(772)
  63 CasesBMI0.001(773)
  63 CasesAbdominal visceral fat0.001(773)
  63 CasesAbdominal subcutaneous fat0.001(773)
  1675 CasesBMI, obesity, body fat (%)0.05(774)
  254 CasesObesity, early onset0.002(775)
  76 CasesFat mass (in Thai men)0.05(776)
  131 CasesFat mass, abdominal visceral fat0.01(777)
  261 CasesBMI0.05(778)
  979 CasesWaist-to-hip ratio, overweight (in men >53 years old)0.05(779)
  802 CasesBMI0.02(780)
  224 CasesBMI (in men)0.02(731)
  49 CasesBMI0.03(781)
  335 CasesWaist-to-hip ratio (in women)0.02(782)
  47 CasesBW (in obese children)0.05(783)
AGRP16q22183 CasesBMI, body fat (%), fat mass (in whites)0.003(784)
  253 CasesBMI0.015(785)
  212 CasesFat mass0.028(785)
  212 CasesBody fat (%)0.013(785)
  874 CasesBody weight0.02(786)
  874 CasesBMI0.01(786)
  874 CasesFat-free mass0.002(786)
  874 CasesFat mass0.04(786)
AGT1q42.2135 CasesBody weight, change0.006(787)
  316 CasesWaist-to-hip ratio0.007(788)
  57 CasesAdipocyte size0.01(789)
  106 CasesAdipocyte size0.02(789)
  94 CasesFat mass (in women >42 years old)0.008(790)
APOA111q23.3482 CasesBMI (in type 2 diabetics)0.048(791)
  482 CasesWaist-to-height ratio (in type 2 diabetics)0.023(791)
APOA21q23.1122 WomenAbdominal visceral fat (white women)0.05(792)
  624 CasesWaist circumference0.03(793)
APOA411q23.3369 CasesBMI0.003(794)
  375 CasesBMI, waist-to-hip ratio (in young men)0.004(795)
  613 CasesBMI, body fat (%)0.004(796)
APOA511q23606 Subjects, 606 womenWeight loss on a 3-month low-fat diet0.0021(797)
APOB2p24.256 CasesBody fat (%), abdominal fat0.04(798)
  232 CasesBMI0.005(799)
  181 CasesBMI0.05(800)
APOC311q23.1-q23.2270 CasesObesity0.05(801)
APOD3q26.2-qter114 CasesBMI0.006(802)
APOE19q13.321775 CasesBMI0.01(803)
  405 CasesFat mass0.002(804)
  405 CasesBody fat (%)0.003(804)
  405 CasesLean mass0.004(804)
  164 CasesWaist circumference (in women with a family history of diabetes)0.05(805)
  64 CasesBody fat (%), leptin (in women)0.02(806)
ARXq11.2-q12131 CasesBMI0.043(807)
  113 CasesWaist circumference (in women)0.002(808)
  294 MenFat-free mass0.027(809)
  112 MenFat-free mass0.049(809)
  106 CasesBody fat (%)0.01(810)
ATP1A21q23.1122 CasesBody fat (%), respiratory quotient0.05(811)
  156 CasesRespiratory quotient (in young adults)0.0001(812)
  12 CasesFat mass0.01(813)
  12 CasesBody weight0.05(813)
BDNF11p13249 SubjectsMinimum lifetime BMI (PO trios with restricting AN)0.019(814)
CAPN102q37.3148 Casesadrb3 activity in adipocytes (in overweight individuals)0.004(815)
  286 CasesBMI0.003(816)
CART5q13.2612 CasesWaist-to-hip ratio (in men)0.002(817)
  528 CasesBMI, obesity0.008(818)
CBFA2T18q21.3281 CasesBMI, body fat (%), waist circumference, hip circumference0.0002(819)
CCKAR4p15.2-p15.11296 CasesLeptin, body fat (%)0.003(820)
CNTFR9p13.2465 CasesFat-free mass0.011(821)
COMT22q11.21246 SubjectsHeight (pre-/early pubertal girls)0.001(822)
  246 SubjectsBody weight (pre-/early pubertal girls)0.009(822)
  246 SubjectsTotal lean mass (pre-/early pubertal girls)0.004(822)
  83 CasesExercise training-induced percentage body fat loss0.05(823)
CRHR117q12-q22503 CasesBMI0.0083(14)
CYP11B28q24.3190 SubjectsBMI (normotensive highlanders from India)0.002(824)
  100 SubjectsBMI (hypertensive highlanders from India)0.004(824)
CYP19A115q21.1125 CasesSagittal abdominal diameter (in women)0.049(825)
  300 CasesBMI0.01(826)
  83 CasesExercise training-induced body fat loss0.01(823)
  83 CasesExercise training-induced percentage body fat loss0.01(823)
CYP2D622q13.111 Cases, 11 menBMI change percentage (white schizophrenic under anti-psychotic)0.01(827)
CYP7A18q12.11102 CasesBMI0.05(828)
DF19p13.324 CasesAbdominal fat (in monozygotic twins)0.05(829)
DIO11p32350 SubjectsFat-free mass0.03(830)
DRD211q23.2392 CasesBody weight0.002(831)
  176 CasesObesity0.002(832)
  320 CasesEnergy expenditure, 24-hour, sleeping metabolic rate0.03(833)
  383 CasesSkinfolds, iliac, skinfolds, triceps0.002(834)
  990 CasesObesity0.03(835)
DRD411p15.5128 Subjects, 128 womenMaximal lifetime BMI (women with seasonal affective disorder)0.001(836)
  103 CasesMaximal lifetime BMI0.007(837)
ENPP16q23.1293 CasesLeptin0.01(838)
  1225 Cases, 1205 controlsObesity (obese children and controls)1e−05(839)
  184 FamiliesObesity0.01(839)
ESR16q25.1108 CasesBMI (in post-menopausal women)0.04(840)
  295 SubjectsBMI0.024(841)
  551 CasesBMI (in middle-aged women)0.05(842)
  551 CasesBody fat (%) (in middle-aged women)0.05(842)
  551 CasesWaist circumference (in middle-aged women)0.05(842)
  216 CasesObesity, android type0.0002(843)
ESR214q23.2295 SubjectsBMI0.02(841)
FABP12p11130 CasesBMI0.05(844)
  130 CasesWaist circumference0.005(844)
FABP24q27714 CasesBMI0.042(845)
  507 CasesBMI, body fat (%)0.01(846)
  120 Subjects, 120 womenTotal abdominal fat (white women)0.004(847)
  120 Subjects, 120 womenSubcutaneous abdominal fat (white women)0.03(847)
  395 CasesAbdominal fat0.008(848)
FASN17q25214 CasesBody fat (%)0.002(849)
  174 CasesRespiratory quotient, 24-hour0.04(849)
  174 Cases24-hour carbohydrate oxidation0.03(849)
FOXC216q22-q24127 Cases, 127 controlsObesity0.027(850)
  223 Cases, 231 controlsObesity0.043(850)
  388 SubjectsBMI (Swedish type 2 diabetics)0.03(851)
  388 SubjectsFat mass (Swedish type 2 diabetics)0.04(851)
  644 CasesBMI0.03(852)
  215 CasesBody fat (%)0.02(852)
  724 CasesWaist-to-hip ratio0.04(853)
GAD210p11.23575 CasesMorbid obesity, eating behavior0.0049(854)
  575 CasesMorbid obesity, eating behavior0.014(854)
  477 Cases, 614 controlsObesity (obese children and controls)0.043(855)
  559 SubjectsBirth weight (obese children)0.009(855)
GCGR17pter950 CasesWaist-to-hip ratio, waist girth, sagittal abdominal diameter0.001(856)
GCK7p15.3-p15.158 CasesBody weight at birth (in men)0.002(857)
GFPT12p13164 Subjects, 164 menFat (%)0.009(858)
GHRHR7p141095 Subjects, 178 familiesObesity0.025(859)
  1418 SubjectsObesity (MONICA Augsburg cohort)0.002(859)
GHRL3p26-p25300 CasesObesity age of onset0.003(860)
  65 CasesBMI (in tall obese children)0.001(861)
  192 CasesObesity (in women)0.05(862)
GNB312p13.31737 CasesObesity (in men)0.01(863)
  294 CasesWeight gain during pregnancy0.006(864)
  230 CasesBMI (in primiparous women)0.01(865)
  20 CasesLipolysis0.01(866)
  111 CasesWeight loss with sibutramine0.0013(867)
  213 CasesBMI, waist circumference, hip circumference, skinfolds (in Nunavut Inuit)0.05(868)
  181 CasesBody weight at birth0.02(869)
  130 CasesBMI0.001(870)
  250 CasesFat mass, change, body fat, change (%)0.006(871)
  114 CasesLipolysis (subcutaneous, adrenoreceptor-mediated)0.004(872)
  197 CasesBMI (in hypertensives)0.02(873)
  1950 CasesBMI, body weight (in men, white, Chinese, and African)0.001(874)
  774 CasesBMI0.03(875)
  774 CasesBody fat (%)0.02(875)
  134 Cases, 80 men, 54 womenWeight change (Chinese schizophrenic under anti-psychotic)0.003(732)
GPR2422q13.2469 Cases, 1127 controlsObesity (French obese children)0.006(876)
  719 Cases, 326 controlsObesity0.0016(877)
GYS119q13.33130 CasesObesity0.03(878)
HSD11B11q32-q41263 CasesBMI (in children)0.005(879)
  263 CasesWaist circumference (in children)0.05(879)
  263 CasesWaist-to-hip ratio (in children)0.05(879)
HSD3B11p11.2132 CasesSkinfolds, sum of six, 12-year change0.04(811)
HSPA1B6p21.31517 CasesObesity0.0002(880)
HTR1B6q14.198 CasesBMI (in women with bulimia nervosa)0.001(881)
HTR2A13q14.11276 CasesDietary energy, carbohydrate and alcohol intake (in obese subjects)0.028(882)
  264 CasesBMI, waist-to-hip ratio, sagittal abdominal diameter0.015(883)
HTR2CXq24293 Cases, 481 controlsObesity0.0001(884)
  224 CasesObesity0.008(885)
  117 CasesBody weight, gain, anti-psychotic-induced0.0003(886)
  148 CasesBody weight, loss (in teenage women)0.0001(887)
  589 CasesBMI0.009(888)
  73 Cases, 45 men, 28 womenWeight change (from 58 white/22 African-American schizophrenic under anti-psychotic)0.05(889)
  42 Cases, 34 men, eight womenBMI change 10% (white schizophrenic under anti-psychotic)0.004(890)
  41 Cases, 26 men, 15 womenBMI change (%) (5 white/35 African American/1 Hispanic schizophrenic under anti-psychotic)0.05(891)
  41 Cases, 26 men, 15 womenBMI change 7% (5 white/35 African American/1 Hispanic schizophrenic under anti-psychotic)0.003(891)
  58BMI change 9 months; white schizophrenic under anti-psychotic0.03(892)
  117BMI change; Chinese schizophrenic under anti-psychotic0.0003(886)
  32BMI change; Chinese schizophrenic under anti-psychotic0.02(893)
IDE10q23-q25724 CasesBMI0.0067(894)
IGF112q23.3502 CasesBody fat (%), fat-free mass, fat mass, change0.05(895)
IGF211p15.52734 CasesBody weight0.01(896)
  1474 CasesBMI0.02(897)
  427 CasesFat mass0.05(898)
  206 WomenFat-free mass0.05(899)
IL67p21271 CasesBMI (in men)0.007(900)
  271 CasesWaist circumference (in men)0.01(900)
  124 CasesFasting energy expenditure0.012(901)
  124 CasesEnergy expenditure during hyperinsulinemic clamp0.007(901)
  3376 CasesBMI0.027(902)
  3376 CasesBody weight change during a 3.5-year follow-up0.03(902)
  242 CasesFat-free mass0.02(903)
  571 CasesBMI0.009(904)
  485 CasesBMI0.003(905)
  74 CasesBMI0.03(905)
IL6R1q22184 CasesObesity (in women)0.05(906)
  700 CasesBMI0.003(907)
  700 CasesBMI0.001(907)
  700 CasesBMI0.004(907)
  700 CasesBMI0.02(907)
  700 CasesBMI0.02(907)
INS11p15.5758 CasesBody weight0.009(908)
  2734 CasesBody weight0.001(896)
  431 CasesBMI0.043(909)
  431 CasesWaist circumference0.015(909)
  238 CasesObesity0.05(910)
  1152 CasesBMI0.0002(911)
  1207 CasesBody weight0.02(912)
  1207 CasesBMI0.03(912)
  1207 CasesWaist circumference0.03(912)
  52 CasesWaist-to-hip ratio (in obese women)0.005(913)
INSR19p13.3-p13.275 CasesObesity (in hypertensives)0.05(914)
IRS12q36.3304 CasesBMI0.001(915)
  304 CasesWaist-to-hip ratio0.001(915)
  156 CasesLeptin (in obese subjects)0.03(916)
  1748 CasesBMI (in African Americans)0.04(917)
IRS213q34233 CasesBMI0.02(918)
  233 CasesBody fat (%)0.01(918)
  233 CasesWaist circumference0.004(918)
LDLR19p13.283 CasesBMI (in normotensives)0.008(919)
  131 CasesBMI, skinfolds, subscapular, skinfolds, triceps, arm fat index0.001(920)
  270 CasesObesity0.02(921)
  84 CasesBMI (in hypertensives)0.004(922)
  112 CasesBMI (in hypertensives)0.04(923)
LEP7q31.3103 CasesBMI, body weight0.005(924)
  395 CasesLeptin0.02(925)
  39 CasesLeptin secretion0.05(926)
  738 CasesObesity0.011(927)
  738 CasesBMI0.028(927)
  233 CasesLeptin (in obese women)0.02(928)
  211 CasesObesity (in women)0.05(929)
  117 CasesLeptin0.04(930)
  168 CasesBody weight, decrease0.006(931)
  84 CasesBody weight0.05(932)
  73 Cases, 55 men, 18 womenBMI change 9 months (white schizophrenic under anti-psychotic)0.03(892)
  128 Cases, 38 controls, 61 men, 67 womenBMI change (Chinese schizophrenic under anti-psychotic)0.003(933)
  128 Cases, 38 controls, 61 men, 67 womenAbdominal subcutaneous fat change (Chinese schizophrenic under anti-psychotic)0.009(933)
LEPR1p31502 CasesBMI, fat mass0.005(934)
  308 CasesFat-free mass0.03(935)
  335 CasesBMI, body weight, fat mass (in women)0.01(936)
  103 SubjectsBody fat (%)0.02(937)
  405 CasesFat mass0.015(938)
  405 CasesLean mass0.002(938)
  179 CasesBMI, fat mass, body weight, loss (in overweight women)0.006(939)
  336 CasesOverweight/obesity0.009(940)
  220 CasesLeptin, BMI, fat mass (in post-menopausal women)0.0001(941)
  267 CasesBMI, sagittal abdominal diameter0.04(942)
  600 CasesBMI > 250.007(943)
  130 CasesObesity, extreme (in children)0.02(944)
  268 CasesEnergy expenditure, 24-hour0.02(945)
  184 CasesAdipocyte size, subcutaneous abdominal0.02(945)
  20 CasesBody fat (%)0.003(946)
  62 CasesAbdominal total fat, abdominal subcutaneous fat0.03(947)
  118 CasesBMI0.01(948)
  770 SubjectsBMI change during 3-year follow-up (STOP-NIDDM trial cohort)0.009(949)
  770 SubjectsWaist circumference change during 3-year follow-up (STOP-NIDDM trial cohort)0.006(949)
LIPC15q21–23230 CasesBMI0.002(950)
  234 CasesWaist circumference0.002(950)
  231 CasesAbdominal visceral fat0.03(950)
  1070 SubjectsBMI0.02(951)
  1070 SubjectsBody fat (%)0.03(951)
LIPE19q13.2257 CasesBMI, body fat (%), fat mass, skinfolds, sum of eight (in white and black women)0.005(952)
  117 CasesWaist-to-hip ratio, lipolysis0.02(953)
  405 CasesObesity (in women)0.05(954)
  405 CasesBody fat (%) (in women)0.05(954)
  380 CasesObesity0.002(955)
  110 CasesBMI (in women)0.012(956)
LMNA1q23.148 CasesLeptin, lipodystrophy, leptin-to-BMI ratio0.05(957)
  306 CasesLeptin, BMI, waist-to-hip ratio (in Canadian Oji-Cree)0.05(958)
  47 CasesFamilial partial lipodystrophy0.0001(959)
  186 CasesBMI, body weight, waist circumference, skinfolds, subscapular0.002(960)
LPL8p21.3587 CasesBMI (in women)0.02(758)
  249 CasesBody fat (%), fat mass, BMI, change (in white women)0.01(961)
  236 CasesBMI0.05(962)
LRPAP14p16.3235 CasesAbdominal obesity0.045(963)
LTA6p21.35630 SubjectsWaist circumference0.009(964)
MACS216p12.31976 CasesBMI0.009(965)
  1976 CasesWaist-to-hip ratio0.0011(965)
MAOAXp11.4-p11.350 CasesBMI > 350.005(966)
MC3R20q13.2-q13.3314 CasesBMI, body fat (%), fat-free mass, fat mass, respiratory quotient (in normal-weight and overweight individuals)0.0005(967)
  244 CasesLeptin (in morbidly obese subjects)0.05(968)
MC4R18q22156 CasesBMI, body fat (%), fat-free mass, fat mass (in women)0.003(969)
  520 CasesObesity0.017(970)
  1135 CasesObesity (in children and adolescents)0.006(33)
  332 SubjectsBMI (offspring of the Quebec Family Study)0.002(971)
  426 CasesSevere obesity0.04(38)
  174 SubjectsWeight loss after bariatric surgery (severely obese patients undergoing bariatric surgery)0.003(972)
  268 CasesBMI, waist-to-hip ratio0.023(973)
  229 CasesResting energy expenditure0.007(974)
MC5R18q22156 CasesBMI, body fat (%), fat-free mass, fat mass (in women)0.002(969)
MED12Xq13.168 CasesObesity0.001(975)
MTTP4q24258 SubjectsAbdominal visceral fat0.005(976)
NCOA320q13.13301 CasesBMI (in post-menopausal women with breast cancer)0.01(977)
NMB15q25291 Subjects6-year change in BMI0.037(978)
  291 Subjects6-year change in waist circumference0.018(978)
  291 Subjects6-year change in percentage body fat0.017(978)
NPR35p14-p13787 CasesBMI0.048(979)
  787 CasesWaist-to-hip ratio0.022(979)
NPY7p15.1595 CasesBMI, waist-to-hip ratio0.03(980)
  907 SubjectsBMI (non-obese Swedish subjects)0.005(981)
  369 CasesBody weight at birth0.03(982)
NPY2R4q31952 CasesBMI0.017(983)
  952 CasesWaist-to-hip ratio0.013(983)
  100 Cases, 67 controls, 167 menSevere obesity (male Pima Indians)0.002(984)
NPY5R4q31-q3274 CasesObesity (in Pima Indians)0.05(985)
NR0B21p35.3294 CasesBody weight at birth0.05(986)
  809 CasesBMI (in 7-year-olds)0.05(986)
  809 CasesWaist circumference (in 7-year-olds)0.01(986)
  305 CasesBMI (in women)0.05(986)
  217 CasesObesity, early onset0.009(987)
NR3C15q3151 CasesAbdominal visceral fat (in lean subjects)0.003(988)
  279 CasesBMI (in obese subjects)0.04(989)
  135 CasesWaist-to-hip ratio (in men)0.01(990)
  262 CasesLeptin, BMI, waist-to-hip ratio, waist circumference0.001(991)
  369 CasesOverweight (in type 2 diabetics)0.003(992)
  83 CasesSkinfolds, sum of (in girls)0.01(993)
  480 CasesAbdominal visceral fat0.001(994)
  12 CasesBody weight, gain0.01(995)
  1963 CasesBMI0.002(996)
  1963 CasesWaist-to-hip ratio0.02(996)
  370 CasesBMI0.05(996)
  337 CasesLean mass0.02(997)
NTRK2 164 SubjectsMinimum lifetime BMI (Spanish eating disorder patients)0.001(998)
PGR11q22.2301 CasesBMI (in post-menopausal women with breast cancer)0.005(977)
PLIN15q26117 CasesLipolysis in adipocytes (in obese women)0.0008(999)
  1538 CasesBMI0.004(1000)
  1538 CasesBMI0.004(1000)
  351 Subjects, 351 womenBody fat (%)0.016(1113)
  351 Subjects, 351 womenBody fat (%)0.014(1113)
  351 Subjects, 351 womenWaist circumference0.02(1113)
  351 Subjects, 351 womenWaist circumference0.045(1113)
  123 Cases, 623 controlsObesity (Malays from Singapore)0.05(1112)
  77 Cases, 521 controlsObesity (Indians from Singapore)0.05(1112)
PNMT17q21.2149 CasesWeight loss (in women)0.006(1002)
POMC2p22-p2175 CasesLeptin (in obese children)0.03(860)
  337 CasesLeptin (in Mexican Americans)0.001(1003)
  118 CasesLeptin (in lean subjects)0.003(1004)
PON17q21.3114 CasesBMI0.045(1005)
PON27q21.3100 CasesBody weight at birth (in Trinidadian neonates and South Asians)0.05(1006)
PPARA22q13.31698 CasesBMI0.023(1007)
  570 CasesBody fat (%)0.028(1007)
  154 CasesBMI (in type 2 diabetics)0.02(1008)
PPARD6p21.2-p21.1178 CasesBMI0.03(1009)
  179 CasesBMI0.04(1009)
PPARG3p25414 CasesBMI0.039(1010)
  921 CasesLeptin, BMI, waist circumference (in Mexican Americans)0.02(1011)
  203 SubjectsBMI (Javanese non-diabetics)0.0016(1012)
  333 CasesBMI (in the middle-aged)0.03(1013)
  973 CasesBMI (in the elderly)0.02(1013)
  422 CasesBMI0.03(1014)
  752 CasesBMI, change (in obese men)0.002(1015)
  869 CasesBMI, change (in lean men)0.008(1015)
  1954 SubjectsBMI over 15 years (whites of the CARDIA study)0.01(1016)
  1954 SubjectsWaist circumference over 15 years (whites of the CARDIA study)0.01(1016)
  1844 SubjectsBMI over 15 years (Blacks of the CARDIA study)0.05(1016)
  464 CasesBMI, obesity0.01(1017)
  619 CasesBMI0.04(1018)
  41 CasesBMI0.02(1019)
  41 CasesFat mass0.02(1019)
  451 CasesBMI (in overweight Blacks)0.02(1020)
  451 CasesWaist-to-hip ratio (in overweight Blacks)0.01(1020)
  451 CasesWaist circumference (in overweight Blacks)0.004(1020)
  1051 SubjectsBMI0.012(1021)
  1051 SubjectsWaist-to-hip ratio0.001(1021)
  1051 SubjectsFat mass0.003(1021)
  1051 SubjectsBody fat (%)0.025(1021)
  228 CasesObesity, morbid0.02(1022)
  119 CasesWeight, increase, 10-year0.009(1023)
  225 CasesWeight, decrease, 3-year0.04(1024)
  140 CasesBMI0.05(1025)
  838 CasesBMI, body weight, waist circumference, height0.002(1026)
  1133 SubjectsBMI0.036(1027)
  820 CasesLeptin (in obese subjects)0.001(1028)
  183 CasesLipid oxidation, 24-hour0.03(1029)
  183 CasesLipid balance, 24-hour0.02(1029)
  70 CasesWeight, increase0.01(1030)
  100 CasesBMI0.0012(1031)
  29 SubjectsEndurance training-induced weight loss (healthy offspring of type 2 diabetics)0.05(1032)
  311 CasesPonderal index at birth0.007(1033)
  311 CasesBody weight gain0.001(1033)
  121 CasesBMI0.03(1034)
  714 CasesBMI0.04(1035)
  596 CasesFat mass0.009(1035)
  685 CasesWaist circumference0.03(1035)
  501 CasesAbdominal visceral fat0.01(1035)
  501 CasesAbdominal subcutaneous fat0.001(1035)
  268 CasesBMI0.022(1036)
  3080 CasesBMI0.037(1037)
  3080 CasesBMI0.036(1037)
  375 CasesObesity, severe, with early onset0.05(1038)
  141 CasesBMI, body weight, fat mass, waist circumference, lean body mass, hip circumference0.002(1039)
PPARGC1A4p15.31467 CasesFat mass (in Austrian women)0.005(1040)
  467 CasesBMI (in Austrian women)0.006(1040)
  467 CasesWaist circumference (in Austrian women)0.01(1040)
  467 CasesHip circumference (in Austrian women)0.03(1040)
  201 CasesAdipocyte size (in Pima Indians)0.04(1041)
  165 CasesLipid oxidation, 24-hour (in Pima Indians)0.03(1041)
  165 CasesLipid balance, 24-hour (in Pima Indians)0.004(1041)
  156 SubjectsBMI0.031(1042)
PTPN120q13.1-q13.21553 CasesBMI0.0146(1043)
  1553 CasesBMI0.018(1043)
  257 CasesBMI0.03(1044)
PTPRF1p34589 CasesBMI0.03(1045)
  589 CasesWaist circumference0.01(1045)
PYY17q21.1100 Cases, 67 controls, 167 menSevere obesity (male Pima Indians)0.001(984)
  6022 SubjectsOverweight0.018(1046)
RETN19p13.2777 CasesBody weight0.005(1047)
  777 CasesWaist circumference0.001(1047)
  777 CasesBMI0.019(1047)
  773 CasesWaist circumference0.026(1047)
  411 CasesBMI, obesity0.0097(1048)
  814 CasesBMI0.01(1049)
  814 CasesWaist circumference0.048(1049)
  12 CasesOverfeeding-induced increase in abdominal visceral fat0.033(1050)
  320 Subjects, 320 womenBMI (women with polycystic ovary syndrome)0.02(1051)
SAH16p13.114059 CasesBMI0.0066(1052)
SCARB112q24.31288 CasesBMI (in healthy lean women)0.004(1053)
  228 CasesObesity, morbid0.002(1022)
SERPINE17q21.3-q221098 CasesAbdominal subcutaneous fat0.0265(1054)
  472 WomenBMI (women from the Quebec Family Study cohort)0.009(1055)
  505 CasesObesity0.002(1056)
SGK6q23263 CasesBMI0.008(1057)
SLC6A14Xq23-q241267 CasesObesity0.0001(1058)
  1267 CasesObesity, eating behavior0.013(1058)
  299 CasesObesity0.0002(1059)
  1805 CasesObesity0.003(1059)
SLC6A35p15.3390 CasesObesity (in black smokers)0.006(1060)
SORBS110q24.1770 CasesObesity0.05(1061)
  114 CasesBMI0.008(1005)
SREBF117p11.2807 CasesObesity0.038(1062)
  807 CasesObesity0.006(1062)
TCF112q24.31203 CasesBMI (in young early onset diabetics)0.0024(1063)
TGFB119q13.31405 CasesLean mass0.002(804)
  284 CasesBMI (in Swedish men)0.05(1064)
  284 CasesSagittal abdominal diameter (in Swedish men)0.05(1064)
TH11p15.52734 CasesBody weight0.0014(896)
TNF6p21.3176 CasesBMI0.01(1065)
  159 CasesBMI0.01(1066)
  159 CasesBody fat (%)0.05(1066)
  159 CasesWaist circumference0.05(1066)
  136 CasesWaist circumference (in women)0.04(1067)
  38 CasesBody fat (%)0.02(1068)
  1351 CasesBMI0.004(1069)
  378 CasesBMI, body fat (%) (in women)0.02(1070)
  1047 CasesObesity0.04(1071)
  363 CasesBMI0.01(1072)
  110 CasesObesity0.02(1073)
TNFRSF1B1p36.21217 CasesLeptin, BMI0.05(1074)
UBL519p13.3396 CasesFat mass0.026(1075)
  396 CasesBody fat (%)0.001(1075)
  396 CasesWaist-to-hip ratio0.034(1075)
UCP14q28-q31163 CasesBody weight, decrease, BMI, decrease0.05(1076)
  526 CasesBMI (in overweight women)0.02(1077)
  162 CasesWaist-to-hip ratio0.003(1078)
  387 SubjectsWaist-to-hip ratio0.008(1079)
  387 SubjectsBody fat (%)0.014(1079)
  113 CasesBody weight (in Japanese women)0.001(1080)
  99 CasesBody weight, change (in pre-menopausal women)0.048(1081)
  22 CasesHigh-fat meal-induced thermogenesis0.01(1082)
  123 CasesFat, increase (in high-weight gainers)0.05(1083)
  172 Subjects, 172 womenObesity0.002(1084)
  24 CasesBody weight, resting metabolic rate0.05(1085)
UCP211q13.360 CasesEnergy expenditure, 24-hour, spontaneous physical activity, 24-hour, sleeping spontaneous physical activity, respiratory quotient, 24-hour non-protein, fat oxidation, 24-hour0.005(1086)
  220 CasesBMI (in South Indian women)0.02(1087)
  791 CasesBMI0.03(1088)
  596 CasesObesity0.007(1088)
  813 CasesObesity0.002(1089)
  949 CasesObesity0.006(1090)
  147 CasesResting energy expenditure0.05(1091)
  147 CasesGlucose oxidation rate at rest0.02(1091)
  147 CasesLipid oxidation rate at rest0.02(1091)
  307 CasesObesity0.01(1092)
  41 CasesBody weight, increase, fat mass, increase (in peritoneal dialysis patients)0.05(1093)
  82 CasesBMI, metabolic rate, 24-hour sleeping (in those >45 years old)0.007(1094)
  63 CasesBMI0.028(1095)
  105 CasesBMI, body fat (%), body weight, fat mass, overweight (%), skinfolds, sum of four0.001(1096)
UCP311q13120 CasesBMI, respiratory quotient, lean body mass, respiratory quotient, non-protein, fat oxidation (in African Americans)0.008(1097)
  116 CasesWaist-to-hip ratio (in South Indian women, in European women)0.03(1098)
  722 CasesFat mass0.004(1099)
  722 CasesLean mass0.013(1099)
  722 CasesBMI0.023(1099)
  722 CasesBody fat (%)0.049(1099)
  419 CasesBMI0.004(1100)
  73 CasesResting energy expenditure (in Black women)0.01(1101)
  734 CasesLeptin, BMI, body fat (%), fat mass, skinfolds, sum of six0.0005(1102)
  393 CasesSkinfolds, sum of eight0.01(1103)
  434 CasesBMI0.01(1104)
  401 CasesBMI (in morbidly obese subjects)0.0037(1105)
  382 CasesBody weight, BMI, current, BMI, maximum0.02(1106)
  24 CasesBody weight, resting metabolic rate0.01(1085)
  64 CasesLeptin, body fat (%) (in women)0.03(806)
VDR12q13.11153 CasesFat mass0.05(1107)
  153 CasesBody weight0.05(1107)
  588 CasesBMI0.009(1108)
  302 CasesBMI0.01(1109)
  302 CasesFat-free mass0.002(1109)
  260 WomenBMI0.042(1110)
  309 CasesBMI (in early onset type 2 diabetics)0.0058(1111)

Associations with BW, BMI, Overweight, and Obesity

BW, BMI, overweight, and obesity were associated with DNA sequence variation in ACE (710, 711), ADIPOQ (718, 719, 720), ADRB2 (744), BDNF (814), COMT (822), CYP11B2 (824), DRD4 (836), ENPP1 (839), ESR1 (841), ESR2 (841), FOXC2 (850, 851), GAD2 (855), GHRHR (859), HTR2C (884), LIPC (951), MC4R (971), MCHR1 (876, 877), NPY (981), NTRK2 (998), NPY2R (984), PLIN (1112), PPARG (1012, 1021, 1027), PPARGC1A (1042), PYY (984, 1046), RETN (1051), SERPINE1 (1055), UCP1 (1084), and VDR (1110).

Associations with Body Composition and Fat Distribution Phenotypes

Body composition-related phenotypes (fat mass, fat-free mass, percentage body fat, sum of skinfolds) showed associations with markers in ACE (712), UCP1 (1079), LEPR (937), LIPC (951), PLIN (1113), PPARG (1021), GFPT1 (858), AR (809), DIO1 (830), IGF2 (899), FOXC2 (850), and COMT (822). Phenotypes reflecting body fat distribution [abdominal visceral and subcutaneous fat, waist-to-hip ratio (WHR), waist circumference, sagittal diameter] were associated with ACE (710), ADIPOQ (719), ADRB2 (744), APOA2 (792), FABP2 (847), LTA (964), MTTP (976), PLIN (1113), PPARG (1021), and UCP1 (1079).

Associations with Changes in BW and Body Composition

Eight studies reported associations between seven candidate genes and changes in BW and body composition. The ADRB1 (736), NMB (978), and PPARG (1016) loci showed associations with spontaneous changes in BW and adiposity over time. Markers in the PPARG (1032) gene were reported to be associated with exercise training-induced weight loss, whereas sequence variation in the APOA5 (797) and MC4R (972) loci modified weight loss in response to a low-fat diet and bariatric surgery, respectively. The ADIPOQ (721) and LEPR (949) loci were reported to be associated with changes in BW during a 3-year diabetes prevention trial with acarbose.

Negative Associations with Obesity-Related Phenotypes

In addition to the positive studies summarized above, we identified 92 studies dealing with 58 genes in which there was no evidence of associations between DNA sequence variations and obesity-related phenotypes. Among these studies, the most frequent ones were those pertaining to markers of PPARG (1012, 1114, 1115, 1116, 1117, 1118, 1119, 1120, 1121, 1122, 1123, 1124, 1125, 1126) (14 studies), ADIPOQ (1127, 1128, 1129, 1130), ADRB3 (1084, 1121, 1131, 1132), IL6 (1129, 1133, 1134, 1135) (four studies each), and ESR1 (1136, 1137, 1138) (three studies). Other markers yielding negative findings were those related to ACE (710, 1032), ACTN (1139), ADIPOR1 (1140), ADIPOR2 (1140), ADRB1 (1132), ADRB2 (1132), AGER (1141), AHSG (1142), APOA4 (1143), APOE (1144, 1145), AR (1146), BDNF (1147), CASQ1 (1148), COL1A1 (1134), CRP (1149), ENPP1 (1150), FABP2 (1151), GNAS (1152), GNB3 (1152, 1153), GPR40 (1154), H6PD (1155), HSD11B1 (1155, 1156), ICAM1 (1157), IGF1 (1158), IL6R (1159), INS (1160, 1161), KCNJ11 (1120), KL (1146), LEP (1129), LEPR (1162), LIPC (1163), LPL (1164), LTA (964), MKKS (1165), MT-DLOOP (1166), MTHFR (1167), MTTP (1168), NOS3 (1169, 1170), NPY (1171), NR0B2 (1172), PARD6A (1173), PLIN (1174), PPARGC1A (1115, 1175), PRDM2 (1176), PTPN1 (1177), SCD (1178), SELE (1179), TAS2R38 (1180), TNF (1181), UCP1 (1084), UCP2 (1182, 1183), UCP3 (1182, 1184), and VDR (1134, 1185).

Drug-Induced BW Gain and Obesity

Unintentional weight gain and weight loss are potential side effects associated with several pharmacological therapies. In previous editions of the human obesity gene map, these studies were summarized within the association studies section. However, because the number of reports addressing the contribution of DNA sequence variation in specific candidate genes to the drug-induced weight changes has increased, these studies will be reviewed in a specific section from now on.

Drug-induced weight gain and obesity have been observed after insulin therapy in patients with type 1 or 2 diabetes; in psychiatric therapy using anti-psychotics, anti-depressants, or mood stabilizers; in neurological treatments with anti-epileptic drugs; and in hypertension or steroid hormone therapies (for review, see (1186)). Drug-induced weight changes could range from a loss of weight to a gain of >50 kg in patients on anti-epileptic, anti-depressant, or anti-psychotic medication (1186). Because modest weight losses of 5% to 10% of initial BW are clinically significant (1187), it is clear that even modest weight gain is an undesirable side-effect of drugs.

Response to anti-psychotic treatment is considered to be a complex trait in which many genes, each with a small effect, are expected to play a role (1188). Few genes have yet to be studied in relation to BW gain under anti-psychotics (Table 4). The functional −759C>T variant (1189) in the serotonin receptor 2C gene (HTR2C) was studied in Chinese anti-psychotic-naïve schizophrenic patients. Carriers of the −759T variant showed three times lower anti-psychotic-induced weight gain than those not carrying the T allele (886). This result was confirmed in anti-psychotic-naïve Chinese men (893) but not in a third sample of anti-psychotic-resistant Chinese (1190). However, in a group of anti-psychotic-resistant African-American, white, and Hispanic individuals, the association of the −759T variant with a smaller weight gain was confirmed recently (891), as in anti-psychotic-naïve whites (892). In contrast, Basile et al. (889) reported that carriers of the −759T allele gained more weight than non-carriers in a mixed population of anti-psychotic-resistant white and African-American patients. A Cys23Ser variant of the HTR2C locus showed no association with BW gain in clozapine-treated anti-psychotic-naïve or resistant schizophrenics of white or African American descent (1191, 1192, 1193).

A significant effect of the cytochrome P450, subfamily IID, polypeptide 6 (CYP2D6) genotypes on the percentage change of BMI was reported in white men taking olanzapine and carrying the poor *4 and intermediate *1/*3 metabolizer genotypes (827, 1194). On the other hand, no association with BW changes in African Americans and whites taking clozapine was observed with a dinucleotide repeat polymorphism of the cytochrome P450 subfamily I, polypeptide 2 (CYP1A2) gene (1191). Chinese anti-psychotic-naïve schizophrenic homozygotes for the A allele of the −2548A>G polymorphism of the LEP gene showed higher changes in BW than patients carrying A/G and G/G genotypes (933). An opposite result was observed in anti-psychotic-naïve whites showing a higher BMI change in homozygotes for the G allele (892). In two recent studies on Chinese schizophrenic patients treated with clozapine, the G/G homozygotes of the −1291C>G variant of the adrenergic α2A receptor (ADRA2A) locus showed a 3 times greater weight gain than the C/C genotype (732). Furthermore, a 2 to 3 times greater weight gain was reported in the TT genotype of the GNB3 825C>T variant in contrast to carriers of the C allele (1195). Negative results were reported previously for these two genes (1191, 1196). Finally, 12 genes showed negative results with anti-psychotic-induced weight changes. Those were the tumor necrosis factor α (1191), the serotonin 1A and 2A receptors, the histamine H1 and H2 receptors, the β3 and α1a-adrenergic receptors (1191, 1192, 1196, 1197), the serotonin transporter and the serotonin receptor 6 (1192), the dopamine receptor 4 (1198), the cytochrome P450 1A2 (CYP1A2), which is different from the CYP2D6 that had shown some association, and the 25-kDa synaptosomal-associated protein (1199).

Treatment with lithium has long been recognized to be associated with adverse metabolic effects, notably weight gain (1200). No evidence for an association has been observed between two polymorphisms (+35A>G in intron 3 and +7T>G in intron 10) in the α subunit of the olfactory G-protein Golf gene and weight gain in response to lithium treatment (1201). The combination of glitazones with insulin may favor weight gain due to enhanced adipogenesis. Patients with the PPARG Pro12Ala genotype show a better response to rosiglitazone treatment than those with the Pro12Pro genotype do, with no difference in weight or BMI (1202).

Human QTLs

Linkage Studies

Linkage studies with obesity-related phenotypes are summarized in Table 5. During the past year, 11 linkage studies were published: nine genome scans, one bivariate linkage analysis of metabolic syndrome phenotypes with markers on chromosome 7q (1203), and a meta-analysis of genome-wide linkage studies for BMI (1204).

Table 5.  Evidence for the presence of linkage with obesity-related phenotypes
Gene/markerLocationPopulationPhenotypesScoreReference
  1. LOD, logarithm of odds; MLS, maximum LOD score; NPL, non-parametric linkage.

D1S4681p36.321249 sibpairs, >10, 000 relative pairsBMILOD = 2.75(1205)
  758 subjects, 53 pedigreesBMILOD = 2.32(1206)
  994 subjects, 37 pedigreesBMILOD = 2.5(1207)
D1S5081p36.23-p36.22994 subjects, 37 pedigreesBMILOD = 2.2(1207)
PGD1p36.22>168 pairsSkinfolds, suprailiacp = 0.03(1208)
D1S5521p36.13893 sibpairsBMI (in whites)LOD = 2.03(1209)
ATCT0511p36320 subjects, 154 familiesBMIMLS = 2.14(1210)
D1S37211p34.1157 subjects, 7 familiesBMI (in whites)p = 0.0099(1211)
D1S1931p34.1202 to 251 pairs, 137 sibships of adult brothers and sistersBMIp = 0.03(1212)
D1S1971p33202 to 251 pairs, 137 sibships of adult brothers and sistersInsulin level, fastingp = 0.05(1212)
D1S2001p32.2202 to 251 pairs, 137 sibships of adult brothers and sistersFat massp = 0.009(1212)
   BMIp = 0.04 
D1S4761p32.2202 to 251 pairs, 137 sibships of adult brothers and sistersInsulin level, integrated, after oral glucose tolerance testp = 0.02(1212)
   BMIp = 0.05 
   Fat massp = 0.02 
   Skinfolds, sum of sixp = 0.02 
LEPR-IVS16CTTT1p31.2268 to 324 pairsFat-free massp = 0.007(935)
   Fat massp = 0.03 
LEPR-IVS3CA1p31.2268 to 324 pairsBMIp = 0.04(935)
   Fat massp = 0.04 
   Skinfolds, sum of sixp = 0.02 
   Fat-free massp = 0.05 
LEPR-Q223R1p31.2268 to 324 pairsFat massp = 0.005(935)
   BMIp = 0.02 
   Skinfolds, sum of sixp = 0.04 
   Fat-free massp = 0.05 
D1S16651p31.1198 subjects, 18 pedigreesLeptinLOD = 3.4(1213)
D1S5501p31.1236 pairsRespiratory quotient, 24-hour (in Pima Indians)LOD = 2.8(1214)
D1S27371p31.1342 familiesTrends in BMI from childhood to adulthoodLOD = 2.2(1215)
LEPR1p31302 subjects, 57 families, 545 sibpairsBlood glucose, fasting (in Mexican Americans)p = 0.018(1216)
   Blood pressure, diastolic (in Mexican Americans)p = 0.003 
D1S16311p21.2514 subjects, 99 families, 347 sibshipsTotal energy intakep = 0.0002(1217)
   Carbohydrate intakep = 0.0026 
   Fat intakep = 2e−05 
AMPD11p13.2514 subjects, 99 families, 347 sibshipsTotal energy intakep = 0.0005(1217)
   Fat intakep = 6e−05 
D1S27261p12342 familiesTrends in BMI from childhood to adulthoodLOD = 2.5(1215)
D1S5341p11.2769 subjects, 182 familiesBMI (in Africans)LOD = 2.24(1218)
  514 subjects, 99 families, 347 sibshipsTotal energy intakep = 0.0008(1217)
   Fat intakep = 0.00038 
  521 subjects, 156 familiesAbdominal subcutaneous fatLOD = 2.3(1219)
S100A11q21514 subjects, 99 families, 347 sibshipsFat intakep = 0.001(1217)
D1S16791q21–1q223027 subjects, 401 families, 317 sibshipsBMI (National Heart, Lung, and Blood Institute Family Heart Study)LOD = 1.8(1220)
D1S3941q21.1514 subjects, 99 families, 347 sibshipsFat intakep = 0.00081(1217)
ATP1A21q23.1582 subjects, 171 families, 289 pairsRespiratory quotientp = 0.02(812)
  295 subjects, 164 familiesAdipocyte sizeLOD = 1.7(1221)
D1S194-D1S1961q23.1-q23.2897 subjects, 179 families, 2127 relative pairsWaist circumferenceMLS = 3.71(1222)
ATP1B11q23.394 pairsRespiratory quotientp = 0.04(811)
D1S2221q31.1514 dubjects, 99 families, 347 sibshipsFat intakep = 0.0002(1217)
D1S4561q32.1313 subjects, 126 families, 99 sibshipsProtein intake (%) (in Blacks)p = 0.0021(1217)
D1S5171q43313 subjects, 126 families, 99 sibshipsSucrose intake (in Blacks)p = 0.0018(1217)
D1S2041q44313 subjects, 126 families, 99 sibshipsSucrose intake (in Blacks)p = 0.0054(1217)
D2S29762p25.32086 subjects, 330 pedigreesWaist circumferenceLOD = 2.06(1223)
D2S29522p25.11297 subjects, 260 familiesWaist circumference, paternalLOD = 2(1224)
D2S14002p25.11297 subjects, 260 familiesBMI, paternalLOD = 2.45(1224)
ACP12p25300 pairsBMIp = 0.004(1225)
  >168 pairsSkinfolds, tricepsp = 0.02(1208)
D2S13602p24.21297 subjects, 260 familiesBMILOD = 1.7(1226)
  3383 subjects, 1124 familiesBody fat (%) (women)LOD = 1.8(1227)
D2S23372p24.1264 sibpairsLeptin (in French whites)LOD = 2(1228)
D2S1652p23.31100 subjects, 170 familiesAdiponectin (in Northern Europeans)LOD = 2.7(1229)
  264 pairsLeptinLOD = 2.4(1230)
D2S3672p23.11100 subjects, 170 familiesAdiponectin (in Northern Europeans)LOD = 2.7(1229)
  264 pairsLeptinLOD = 2.7(1230)
D2S17882p22.35000 relative pairsLeptinLOD = 4.9(1231)
   Fat massLOD = 2.8 
  337 subjectsLeptinLOD = 7.5(1003)
  1778 sibshipsBMIp = 0.0006(1232)
  349 subjects, 66 pedigreesBMI (in whites)LOD = 3.08(1233)
  720 subjects, 230 familiesLeptinp = 0.008(1234)
   BMIp = 0.008 
D2S13462p22-p21816 subjects, 42 familiesTotal energy intakeLOD = 2(1235)
   Protein intakeLOD = 2.22 
   Fat intakeLOD = 2.09 
   Saturated fat intakeLOD = 2.62 
D2S13562p22-p211778 sibshipsBMIp = 0.0004(1232)
D2S13522p16.31778 sibshipsBMIp = 0.0004(1232)
D2S27392p16321 relative pairsBody fat (%)LOD = 3.3(1236)
D2S2739-D2S4412p16-2p13.3321 relative pairsFat massLOD = 2.56(1236)
D2S4412p13.3453 subjects, 99 familiesAbdominal subcutaneous fatLOD = 1.88(1237)
IGKC2p11.2>168 pairsSkinfolds, tricepsp = 0.03(1208)
D2S293-D2S3832q12.2-2q14.3430 subjects, 27 sibpairs, 27 pedigreesBMILOD = 2.9(1238)
D2S1602q131249 sibpairs, >10, 000 relative pairsBMILOD = 2.56(1205)
D2S4102q14.12086 subjects, 330 pedigreesWaist circumferenceLOD = 2(1223)
D2S3472q14.31249 sibpairs, >10, 000 relative pairsBMILOD = 4.04(1205)
   Body fat (%)LOD = 1.91 
   Fat massLOD = 2.03 
  758 subjects, 53 pedigreesBMILOD = 3.42(1206)
D2S13342q21.3453 subjects, 99 familiesAbdominal visceral fatLOD = 1.97(1237)
D2S13992q23.3453 subjects, 99 familiesAbdominal visceral fatLOD = 2.3(1237)
D2S112-D2S3962q33.2-2q36.3506 subjects, 115 pedigreesBMI > 99th percentileLOD = 2.73(1239)
   BMI > 97th percentileLOD = 2.08 
D2S4342q35453 subjects, 99 familiesAbdominal visceral fatLOD = 2.5(1237)
D2S1363-D2S12792q35-2q36.32467 subjects, 387 familiesBMILOD = 2.4(1240)
   Waist-to-hip ratioLOD = 1.72 
   Subscapular skinfoldLOD = 2.55 
D3S23873p26.3320 subjects, 154 familiesBMIMLS = 3.67(1210)
  215 subjects, 105 familiesAbdominal subcutaneous fatLOD = 2.16(1237)
D3S12593p25.21055 pairsBMILOD = 2(1241)
D3S36083p25.2624 subjects, 28 familiesEating behavior, restraint (in Old Order Amish)LOD = 2.5(1242)
D3S24033p241297 subjects, 260 familiesBody fat (%), maternalLOD = 2.2(1224)
D3S30383p24.3893 sibpairsBMI, paternal effect (in whites)p = 0.0065, LOD = 1.77(1209)
D3S24323p22.3377 pairsBody fat (%) (in Pima Indians)LOD = 2(1243)
D3S17683p22.2580 familiesBMILOD = 3.4(1244)
Chr3p-region3p141848 subjects, 279 pedigreesBMILOD = 1.9(1245)
   BMI and systolic blood pressureLOD = 2.13 
   BMI and diastolic blood pressureLOD = 2.36 
D3S24063p12.23383 subjects, 1124 familiesBMI (men)LOD = 2(1227)
D3S30453q12.31297 subjects, 260 familiesBMI, paternalLOD = 3.66(1224)
  1297 subjects, 260 familiesBMI ≥ 30NPL = 1.88(1246)
  1297 subjects, 260 familiesBMI ≥ 30NPL = 1.88(1226)
Chr3q-region3q13.31848 subjects, 279 pedigreesBMI and systolic blood pressure and diastolic blood pressure (trivariate)LOD = 2.59(1245)
ATA28H113q13.333383 subjects, 1124 familiesBMI (men)LOD = 2.3(1227)
   Body fat (%) (men)LOD = 2.6 
   BMI (men and women)LOD = 2.8 
D3S17643q22.1596 subjects, 158 familiesFactor central obesityMLS = 2.61(1247)
  1055 pairsBMILOD = 3.4(1241)
D3S17443q231778 sibshipsBMIp = 0.0009(1232)
D3S30533q261778 sibshipsBMIp = 0.0015(1232)
D3S24273q26.332209 subjects, 507 familiesBMILOD = 3.3(1248)
   Waist circumferenceLOD = 2.4 
  3383 subjects, 1124 familiesBMI (men)LOD = 1.7(1227)
  545 subjects, 128 familiesBMI (in African Americans)LOD = 4.3(1249)
  1055 pairsBMILOD = 3.4(1241)
  618 subjects, 202 familiesBMILOD = 1.8(1250)
D3S36763q26.33545 subjects, 128 familiesBMI (in African Americans)LOD = 4.3(1249)
D3S12623q27.33383 subjects, 1124 familiesBody fat (%) (men)LOD = 2.4(1227)
D3S13113q29215 subjects, 105 familiesAbdominal subcutaneous fatLOD = 2.5(1237)
D4S9124p16.1430 subjects, 27 sibpairs, 27 pedigreesBMILOD = 4.5(1238)
D4S26394p15.32994 subjects, 37 pedigreesBMILOD = 2.2(1207)
D4S22894p15.31994 subjects, 37 pedigreesBMILOD = 2.6(1207)
D4S23974p15.2521 subjects, 156 familiesAbdominal subcutaneous fatLOD = 2.4(1219)
D4S33504p15.1994 subjects, 37 pedigreesBMILOD = 9.2(1207)
D4S26324p15.1994 subjects, 37 pedigreesBMIMLS = 6.1(1207)
D4S16274p13994 subjects, 37 pedigreesBMILOD = 3.4(1207)
D4S30194q12994 subjects, 37 pedigreesBMILOD = 2.1(1207)
D4S15924q121249 sibpairs, >10, 000 relative pairsBMILOD = 2.29(1205)
D4S32484q13.1994 subjects, 37 pedigreesBMILOD = 2(1207)
D4S16474q2459 pedigrees, 277 sibshipsBMILOD = 2.63(1251)
D4S1647-D4S26234q24-4q25321 sibpairsBody fat (%)LOD = 2.39(1236)
D4S16444q28.31297 subjects, 260 familiesBMILOD = 1.71(1226)
  1297 subjects, 260 familiesBMILOD = 1.71(1246)
D4S24174q31.1893 sibpairsBMI, paternal effect (in whites)p = 0.005, LOD = 1.84(1209)
  521 subjects, 156 familiesAbdominal subcutaneous fatLOD = 1.8(1219)
GYPA4q31.1160 pairsSkinfolds, trunk-to-extremity ratiop = 0.02(1252)
D4S16294q32.1893 sibpairsBMI, maternal effect (in whites)p = 0.005, LOD = 1.89(1209)
D4S4064q34.1447 subjects, 109 pedigreesBMI > 35LOD = 2.55(1253)
D4S24314q34.1215 subjects, 105 familiesAbdominal subcutaneous fatLOD = 2.3(1237)
D5S8175p15.21100 subjects, 170 familiesAdiponectin (in Northern Europeans)LOD = 4.1(1229)
  618 subjects, 202 familiesBMILOD = 1.9(1250)
D5S4265p13.3264 pairsLeptinLOD = 2.9(1230)
D5S24895p13.21526 pairsBMI (in Pima Indians)LOD = 1.7(1254)
ISL15q11.2226 pairsObesityp = 0.03(1255)
   Leptinp = 0.0004 
   BMIp = 0.0004 
D5S4075q11.21249 sibpairs, >10, 000 relative pairsFat-free massLOD = 1.59(1205)
D5S25005q12.11526 pairsBMI (in Pima Indians)LOD = 1.7(1254)
D5S17255q14.3321 sibpairsFat massLOD = 2.25(1236)
   Body fat (%)LOD = 2.56 
D5S14635q14.3447 subjects, 109 pedigreesBMI > 27LOD = 2.68(1253)
D5S14535q21.3342 familiesTrends in BMI from childhood to adulthoodLOD = 2(1215)
D5S15055q23.1342 familiesLong-term burden in BMILOD = 2.2(1215)
D5S6585q31.3453 subjects, 99 familiesAbdominal subcutaneous fatLOD = 2.06(1237)
   Abdominal total fatLOD = 1.84 
NR3C15q3188 pairsBMIp = 0.009(1256)
D5S14805q32453 subjects, 99 familiesAbdominal total fatLOD = 2.1(1237)
D5S820-D5S14565q33.2-5q35.1729 subjects, 275 familiesAbdominal subcutaneous fatMLS = 2.64(1210)
D5S14715q35.1893 sibpairsBMI (in whites)p = 0.0006, LOD = 2.48(1209)
D5S2115q35.23027 subjects, 401 families, 317 sibshipsBMI (National Heart, Lung, and Blood Institute Family Heart Study)LOD = 1.8(1220)
  2072 subjects, 407 familiesFactor central obesityMLS = 1.87(1247)
D5S4085q35.3157 subjects, 7 familiesBMI (in whites)p = 0.0039(1211)
SE306p25.1803 subjects, 192 familiesBMILOD = 2.13(1257)
  596 subjects, 158 familiesFactor central obesityMLS = 2.07(1247)
D6S24346p23596 subjects, 158 familiesFactor central obesityMLS = 1.94(1247)
D6S2606p23508 subjects, 21 familiesObesity under anti-psychoticsLOD = 1.72(1258)
D6S19596p22.3-p22.2618 subjects, 202 familiesBody fat (%)LOD = 2.7(1250)
D6S2766p22.1624 subjects, 28 familiesEating behavior, restraint (in Old Order Amish)LOD = 2.3(1242)
BF6p21.31>168 pairsSkinfolds, subscapularp = 0.01(1208)
   Skinfolds, tricepsp = 0.01 
   Skinfolds, suprailiacp = 0.01 
GLO16p21.3-p21.1>168 pairsBody weightp = 0.004(1259)
   Skinfolds, suprailiacp = 0.004 
TNF6p21.3>255 pairs, 304 sibpairsBody fat (%) (in Pima Indians)p = 0.002(1072)
D6S2716p21.11199 pairsLeptinLOD = 2.1(1260)
D6S4626q22.31447 subjects, 109 pedigreesBMI > 35LOD = 2.49(1253)
D6S462-D6S4416q22.31-6q23.2506 subjects, 115 pedigreesBMI > 97th percentileLOD = 3.27(1239)
   BMI > 95th percentileLOD = 3.13 
D6S10096q23.32086 subjects, 330 pedigreesWaist circumferenceLOD = 3.3(1223)
  330 pedigrees, 1702 sibshipsBMILOD = 2.79(1261)
D6S4036q23.3261 subjects, 27 pedigrees(BMI, leptin, fasting specific insulin) (in Mexican Americans)LOD = 4.2(1262)
D6S10036q24.1261 subjects, 27 pedigrees(BMI, leptin, fasting specific insulin) (in Mexican Americans)LOD = 4.2(1262)
D6S2646q27261 subjects, 27 pedigrees(Systolic blood pressure, diastolic blood pressure) (in Mexican Americans)LOD = 4.9(1262)
D6S2816q271249 sibpairs, >10, 000 relative pairsBMILOD = 1.77(1205)
   Fat massLOD = 2.02 
D7S24777p22.3349 subjects, 66 pedigreesBMI (in whites)LOD = 2.53(1233)
D7S18197p22.2349 subjects, 66 pedigreesBMI (in whites)LOD = 2.53(1233)
D7S25577p21.2342 familiesLong-term burden in BMILOD = 2.9(1215)
D7S30517p21.11055 pairsBMILOD = 2.7(1241)
D7S18027p15.3803 subjects, 192 familiesBMILOD = 2.4(1257)
NPY7p15.1302 subjects, 57 families, 545 sibpairsObesity (in Mexican Americans)p = 0.042(1216)
   Body weight (in Mexican Americans)p = 0.02 
   Abdominal circumference (in Mexican Americans)p = 0.031 
   Hip circumference (in Mexican Americans)p = 0.012 
   Diastolic blood pressure (in Mexican Americans)p = 0.005 
   Body mass, body size (in Mexican Americans)p = 0.048 
D7S18087p15.1336 sibpairs, 609 relative pairsFat-free massLOD = 2.72(1263)
D7S8177p14.3769 subjects, 182 familiesBMI (in Africans)LOD = 3.83(1218)
D7S4847p14.2342 familiesLong-term burden in BMILOD = 2.4(1215)
D7S18187p12.3342 familiesTrends in BMI from childhood to adulthoodLOD = 2.2(1215)
D7S506-D7S6537p11.2-7q11.22430 subjects, 27 sibpairs, 27 pedigreesBMILOD = 1.9(1238)
D7S30467q11.22514 subjects, 99 families, 347 sibshipsProtein intake (%)p = 0.0012(1217)
D7S6537q11.22440 subjects, 27 familiesBivariate BMI: high-density lipoproteinMLS = 3.86(1203)
   Bivariate BMI: triglyceridesMLS = 4.21 
   Bivariate waist circumference: high-density lipoproteinMLS = 3.47 
   Bivariate waist circumference: triglyceridesMLS = 3.74 
   Bivariate BMI: insulinMLS = 2.44 
   Bivariate waist circumference: insulinMLS = 1.86 
   Bivariate BMI: waist circumferenceMLS = 2.98 
D7S653-D7S4797q11.22-7q22.1440 subjects, 27 familiesBMIMLS = 2.4(1203)
   Waist circumferenceMLS = 2 
D7S8217q21.31297 subjects, 260 familiesBMI ≥ 35NPL = 1.93(1226)
D7S4797q22.1261 subjects, 27 pedigreesHigh-density lipoprotein, in triglycerides (in Mexican Americans)LOD = 3.2(1262)
D7S17997q22.11297 subjects, 260 familiesBMI ≥ 35NPL = 2.25(1226)
  1297 subjects, 260 familiesBMI > 27NPL = 2.52(1246)
   BMI > 30NPL = 2.04 
   BMI > 35NPL = 2.25 
D7S6927q22.31020 subjects, 200 familiesBMI (in whites)p = 0.0002, LOD = 2.75(1264)
D7S5237q31.11020 subjects, 200 familiesBMI (in whites)p = 0.0009, LOD = 2.11(1264)
D7S4717q31.1261 subjects, 27 pedigreesHigh-density lipoprotein, in triglycerides (in Mexican Americans)LOD = 3.2(1262)
LEP7q31.3302 subjects, 57 families, 545 sibpairsWaist-to-hip ratio (in Mexican Americans)p = 0.01(1216)
   Cholesterol, total (in Mexican Americans)p = 0.03 
   Cholesterol, high-density lipoprotein (in Mexican Americans)p = 0.026 
  47 pairs, 47 healthy female/female dizygotic twinsbody fatp = 0.008(1265)
D7S28477q31.311055 pairsBMILOD = 2.4(1241)
D7S6807q32.260 pairsBMIp = 0.002(1266)
D7S5147q32.260 pairsBMIp = 0.002(1266)
  545 pairsBMI (in Mexican Americans)p = 0.0001(1267)
   Skinfolds, extremity (in Mexican Americans)p = 0.0001 
   Waist circumference (in Mexican Americans)p = 0.0001 
   Fat mass (in Mexican Americans)p = 0.0001 
D7S5047q32.246 pairs, 103 affected sibpairsBMI (in African Americans)p = 0.001(1268)
  78 families, 59 pairsBMIp = 0.04(1269)
D7S18757q32.2302 subjects, 57 families, 545 sibpairsWaist-to-hip ratio (in Mexican Americans)p = 0.009(1216)
  521 subjects, 156 familiesAbdominal subcutaneous fatLOD = 2(1219)
  88 trios (index probands and both parents)BMI (in German children and adolescents)p = 0.04(1270)
D7S5307q32.360 pairsBMIp = 0.002(1266)
D7S18047q32.33027 subjects, 401 families, 317 sibshipsBMI (National Heart, Lung, and Blood Institute Family Heart Study)MLS = 4.9, p < 0.00001(1220)
D7S6407q33672 subjects, 28 pedigreesLeptin (in Old Order Amish)LOD = 1.9 adjusted for BMI(1271)
D7S4957q34545 pairsBMI (in Mexican Americans)p = 0.0001(1267)
   Skinfolds, extremity (in Mexican Americans)p = 0.0001 
   Fat mass (in Mexican Americans)p = 0.0001 
   Waist circumference (in Mexican Americans)p = 0.0001 
D7S18247q34157 subjects, 7 familiesBMI (in whites)p = 0.0008(1211)
KEL7q35160 pairsBMIp = 0.0001(1252)
   Skinfolds, sum of sixp = 0.0001 
D7S21957q35157 subjects, 7 familiesBMI (in whites)p = 0.001(1211)
D7S30687q35157 subjects, 7 familiesBMI (in whites)p = 0.004(1211)
D7S6367q36.1672 subjects, 28 pedigreesLeptin (in Old Order Amish)LOD = 1.9 adjusted for BMI(1271)
D7S30707q36.13383 subjects, 1124 familiesBody fat (%) (men)LOD = 1.8(1227))
  215 subjects, 105 familiesAbdominal total fat training responseLOD = 2.5(1237)
Chromosome 8 region8pter-p23.32814 subjects, 505 familiesBMIp = 4.6e−05(1204)
D8S2648p23.32072 subjects, 407 familiesFactor central obesityMLS = 1.92(1247)
D8S2778p23.1893 sibpairsBMI, paternal effect (in whites)p = 0.003, LOD = 1.98(1209)
GATA151F028p22769 subjects, 182 familiesBMI (in Africans)LOD = 2.34(1218)
D8S5498p221249 sibpairs, >10, 000 relative pairsFat massLOD = 1.95(1205)
D8S2828p21.3994 subjects, 37 pedigreesBMILOD = 2(1207)
D8S11218p11.23470 subjects, 10 familiesBMIp = 0.0001, MLS = 3.21(1272)
D8S11108q11.225000 sibpairsLeptinLOD = 2.2(1231)
D8S1110-D8S11138q11.22-8q12.1729 subjects, 275 familiesAbdominal subcutaneous fatMLS = 2.24(1210)
D8S11138q12.1893 sibpairsBMI (in whites)p = 0.0013, LOD = 2.05(1209)
D8S23248q13.31297 subjects, 260 familiesBMI ≥ 35NPL = 1.9(1226)
  1297 subjects, 260 familiesBMI ≥ 35NPL = 1.9(1246)
GATA8B018q21.359 pedigrees, 277 sibshipsBMILOD = 2.56(1251)
D8S11368q22.3508 subjects, 21 familiesObesityMLS = 1.93(1258)
D8S5568q23.1522 subjects, 99 families, 364 sibpairsBMI (in whites)LOD = 2(1273)
D8S11328q23.1157 subjects, 7 familiesBMI (in whites)p = 0.005(1211)
D8S11798q24.11729 subjects, 275 familiesWaist-to-hip ratioMLS = 2.06(1210)
D9S9109q22.331297 subjects, 260 familiesBMI ≥ 30, maternalLOD = 2.28(1224)
  1297 subjects, 260 familiesBMI > 30NPL = 2.09(1246)
  1297 subjects, 260 familiesBMI ≥ 30NPL = 2.09(1226)
D9S11229q21-q22521 subjects, 156 familiesAbdominal subcutaneous fatLOD = 2.4(1219)
D9S2579q22.1521 subjects, 156 familiesAbdominal subcutaneous fatLOD = 2.4(1219)
D9S299-D9S9309q31-9q31430 subjects, 27 sibpairs, 27 pedigreesBMILOD = 2.1(1238)
ORM19q33.1>168 pairsSkinfolds, suprailiacp = 0.03(1208)
D9S2829q34508 subjects, 21 familiesObesity under anti-psychoticsLOD = 1.71(1258)
AK19q34.13>168 pairsSkinfolds, suprailiacp = 0.01(1208)
D9S1589q34.3522 subjects, 99 families, 364 sibpairsBMI (in whites)LOD = 2.3(1273)
D10S143510p15.3522 subjects, 99 families, 364 sibpairsBMI (in whites)LOD = 2.7(1273)
   Fat mass (in whites)LOD = 2.7 
  1526 pairsBMI (in Pima Indians)LOD = 1.7(1254)
D10S18910p15.1522 subjects, 99 families, 364 sibpairsBMI (in whites)MLS = 2.7, SEGPATH(1273)
   Fat mass (in whites)MLS = 1 
  1526 pairsBMI (in Pima Indians)LOD = 1.7(1254)
D10S142310p12.33893 sibpairsBMI, paternal effect (in whites)p = 0.005, LOD = 1.89(1209)
D10S58210p12.31667 subjects, 244 familiesObesity (in whites and African Americans)NPL = 2.68(1274)
  862 subjects, 170 familiesObesity (in African Americans, in European Americans)p = 0.0005(1275)
D10S19710p12.21297 subjects, 260 familiesBMI ≥ 27, maternalLOD = 2.71(1224)
  264 pairsObesityLOD = 4.9(1230)
  369 subjects, 89 familiesObesity (in white children and adolescents)LOD = 2.24(1276)
D10S20410p12.1386 subjects, 93 familiesObesityLOD = 2.5(1277)
D10S19310p12.1386 subjects, 93 familiesObesityLOD = 2.5(1277)
D10S20810p11.23667 subjects, 244 familiesObesity (in whites and African Americans)NPL = 2.68(1274)
  862 subjects, 170 familiesObesity (in African Americans, in European Americans)p = 0.0005(1275)
D10S178110p11.2386 subjects, 93 familiesObesityLOD = 2.5(1277)
SHGC-3148010p11.23386 subjects, 93 familiesObesityLOD = 2.5(1277)
D10S22010q21.1672 subjects, 28 pedigreesLeptin (in Old Order Amish)LOD = 2.7(1271)
D10S10710q21.1862 subjects, 170 familiesObesity (in African Americans, in European Americans)p = 0.0005(1275)
D10S164610q22.1667 subjects, 244 familiesWaist circumference (in whites and African Americans)LOD = 2.5(1274)
   BMI (in whites and African Americans)NPL = 2.24 
D10S53510q22.3667 subjects, 244 familiesWaist circumference (in whites and African Americans)LOD = 2.5(1274)
   BMI (in whites and African Americans)NPL = 2.24 
D10S126710q24.32447 subjects, 109 pedigreesBMI > 27LOD = 2.47(1253)
D10S167910q26.13667 subjects, 244 familiesWaist-to-hip ratio (in whites and African Americans)NPL = 2.22(1274)
   Obesity (in whites and African Americans)NPL = 2.25 
D10S165610q26.2667 subjects, 244 familiesWaist-to-hip ratio (in whites and African Americans)NPL = 2.22(1274)
   Obesity (in whites and African Americans)NPL = 2.25 
Chr10q-region10q26.31848 subjects, 279 pedigreesBMILOD = 1.98(1245)
   BMI and systolic blood pressureLOD = 2.55 
   BMI and diastolic blood pressureLOD = 3.2 
   BMI and systolic blood pressure and diastolic blood pressureLOD = 4.09 
D10S21210q26.359 pedigrees, 277 sibshipsBMILOD = 2.08(1251)
  198 subjects, 18 pedigreesBMILOD = 3.3(1213)
D11S984-D11S98811p15.5-11p15.5430 subjects, 27 sibpairs, 27 pedigreesBMILOD = 2.5(1238)
CCKBR11p15.4226 pairsLeptinp = 0.01(1255)
C11P15_311p15.2215 subjects, 105 familiesAbdominal subcutaneous fatLOD = 1.85(1237)
D11S41911p15.267 pairsBMI (in French whites)p = 0.003(708)
ATA34E0811p133383 subjects, 1124 familiesBMI (Women)LOD = 1.8(1227)
  215 subjects, 105 familiesAbdominal subcutaneous fatLOD = 1.75(1237)
D11S199311q121297 subjects, 260 familiesBody fat (%), paternalLOD = 2.21(1224)
D11S131311q12.1369 subjects, 89 familiesObesity (in white children and adolescents)LOD = 1.65(1276)
D11S2006-D11S237111q12.13-11q13.3729 subjects, 275 familiesAbdominal visceral fatMLS = 2.36(1210)
D11S91611q13.3640 subjects, 240 relative pairs, 155 pedigreesResting metabolic ratep = 0.006(1278)
D11S237111q13.31297 subjects, 260 familiesBody fat (%), paternalLOD = 2(1224)
D11S132111q13.3640 subjects, 240 relative pairs, 155 pedigreesResting metabolic ratep = 0.02(1278)
   Body fat (%)p = 0.04 
   Fat massp = 0.02 
D11S91111q13.4640 subjects, 240 relative pairs, 155 pedigreesResting metabolic ratep = 2e−06(1278)
D11S200211q13.31510 subjects, 509 familiesFactor central obesityMLS = 2.19(1247)
D11S940-D11S200011q22-11q22.3562 subjects, 178 familiesBMILOD = 2.5(1279)
D11S200011q22.3769 subjects, 182 familiesBMI (in Africans)LOD = 3.35(1218)
  277 siblingsBody fat (%) (in Pima Indians)p = 0.0028(1243)
  157 subjects, 7 familiesBMI (in whites)p = 0.0079(1211)
D11S236611q23.1277 siblingsBody fat (%) (in Pima Indians)p = 0.0009(1243)
D11S199811q23.31526 pairsBMI (in Pima Indians)LOD = 2.7(1254)
D11S97611q23.3236 pairsEnergy expenditure, 24-hour (in Pima Indians)LOD = 2(1214)
D11S446411q24.1430 subjects, 27 sibpairs, 27 pedigreesBMILOD = 2.3(1238)
  1526 pairsBMI (in Pima Indians)LOD = 2.7(1254)
  1778 sibshipsBMIp = 0.0023(1232)
  994 subjects, 37 pedigreesBMILOD = 2.8(1207)
D11S93411q24.2994 subjects, 37 pedigreesBMILOD = 2.6(1207)
D11S91211q24.3264 families, 1766 pairs, 966 siblingsBMILOD = 3.6(1280)
  1778 sibshipsBMIp = 0.0003(1232)
  994 subjects, 37 pedigreesBMILOD = 2.7(1207)
D11S235911q251778 sibshipsBMIp = 0.0012(1232)
GATA49D12N (D3S2395)12p13.311297 subjects, 260 familiesBMI ≥ 27NPL = 2.12(1226)
  893 sibpairsBMI, paternal effect (in whites)p = 0.006, LOD = 1.83(1209)
  1297 subjects, 260 familiesBMI ≥ 27NPL = 2.12(1246)
D12S39112p13.2342 familiesTrends in BMI from childhood to adulthoodLOD = 2.9(1215)
D12S104212p12.1522 subjects, 99 families, 364 sibpairsBMI (in whites)MLS = 2.1(1273)
   Fat mass (in whites)MLS = 1.2 
D12S297-D12S129412q13.13-12q15729 subjects, 275 familiesWaist-to-hip ratioMLS = 2.67(1210)
D12S8312q13.31249 sibpairs, >10, 000 relative pairsFat-free massLOD = 1.79(1205)
D12S169112q14.1514 subjects, 99 families, 347 sibshipsFat intakep = 0.0013(1217)
D12S105212q21729 subjects, 275 familiesWaist-to-hip ratioMLS = 2.6(1210)
  349 subjects, 66 pedigreesBMI (in whites)LOD = 3.41(1233)
D12S1052-D12S106412q21-12q21.33729 subjects, 275 familiesWaist-to-hip ratioMLS = 2.91(1210)
D12S106412q21.33342 familiesTrends in BMI from childhood to adulthoodLOD = 2.1(1215)
  349 subjects, 66 pedigreesBMI (in whites)LOD = 3.41(1233)
PAH12q22-q24.21297 subjects, 260 familiesBMI > 30NPL = 1.92(1246)
PAH-D12S207012q22-q24.2-12q24.21729 subjects, 275 familiesWaist-to-hip ratioMLS = 2.48(1210)
D12PAH12q23.1342 familiesTrends in BMI from childhood to adulthoodLOD = 2.3(1215)
   Long-term burden in BMILOD = 3 
  1297 subjects, 260 familiesBMI ≥ 30NPL = 1.92(1226)
D12S79-D12S136612q23.1-12q24.23508 subjects, 21 familiesObesity under anti-psychoticsMLS = 2.74(1258)
IGF112q23.3521 subjects, 156 familiesAbdominal subcutaneous fatLOD = 1.9(1219)
  502 subjects, 99 families, 352 pairs, 190 parents, 312 offspringAbdominal visceral fat (in whites)p = 0.02(895)
   Fat-free mass (in whites)p = 0.0002 
D12S133912q24.21297 subjects, 260 familiesBody fat (%)LOD = 4.08(1246)
D12S207012q24.21514 subjects, 99 families, 347 sibshipsFat intake (%)p = 0.002(1217)
  1297 subjects, 260 familiesBMI, maternalMLS = 4.01(1224)
   Waist circumference, maternalMLS = 3.69 
  1297 subjects, 260 familiesBody fat (%)LOD = 3.79(1226)
  1297 subjects, 260 familiesBMILOD = 3.57(1246)
   Waist circumferenceLOD = 3.05 
D12S395-D12S207812q24-12q24.323383 subjects, 1124 familiesBody fat (%) (women)LOD = 3.8(1227)
D12S207812q24.32521 subjects, 156 familiesAbdominal subcutaneous fatLOD = 2.9(1219)
D12S2078-D12S104512q24.32- 12q24.333383 subjects, 1124 familiesBody fat (%) (men and women)LOD = 3.3(1227)
D12S104512q24.33521 subjects, 156 familiesAbdominal subcutaneous fatLOD = 2.9(1219)
D12S163812q24.3359 pedigrees, 277 sibshipsBMILOD = 1.94(1251)
D13S17513q12.11580 familiesBMILOD = 3.3(1244)
D13S22113q12.13580 familiesBMILOD = 3.3(1244)
D13S149313q13.21297 subjects, 260 familiesBMI ≥ 40NPL = 2.03(1226)
  3383 subjects, 1124 familiesBMI and blood pressure response to postural changeLOD = 3.2(1281)
D13S89413q13.31297 subjects, 260 familiesBMI ≥ 27, maternalLOD = 2.34(1224)
  1297 subjects, 260 familiesBMI ≥ 40NPL = 2.63(1226)
  1297 subjects, 260 familiesBMI ≥ 27NPL = 1.88(1246)
ESD13q14.11160 pairsBody fat (%)p = 0.04(1252)
   Skinfolds, sum of sixp = 0.04 
D13S25713q14.23027 subjects, 401 families, 317 sibshipsBMI (National Heart, Lung, and Blood Institute Family Heart Study)MLS = 3.2 p = 0.00006(1220)
D13S180713q21.11297 subjects, 260 familiesBMILOD = 2.67(1226)
D13S80013q21.32342 familiesTrends in BMI from childhood to adulthoodLOD = 2(1215)
  1297 subjects, 260 familiesBMILOD = 2.7(1226)
  1297 subjects, 260 familiesBMILOD = 2.7(1246)
D13S79313q31.31297 subjects, 260 familiesBMI, paternalLOD = 4.79(1224)
   Waist circumference, paternalLOD = 3.11 
  1297 subjects, 260 familiesBMILOD = 2.78(1226)
  1312 subjects, 696 familiesFactor central obesityMLS = 2.17(1247)
D13S77913q32.21297 subjects, 260 familiesBMILOD = 2.82(1226)
  1312 subjects, 696 familiesFactor central obesityMLS = 2.67(1247)
  1297 subjects, 260 familiesBMILOD = 2.82(1246)
   Waist circumferenceLOD = 1.8 
D13S28513q34330 pedigrees, 1702 sibshipsObesity before age 35p = 0.001(1282)
  521 subjects, 156 familiesAbdominal subcutaneous fatLOD = 1.9(1219)
D14S74214q11.2522 subjects, 99 families, 364 sibpairsFat mass (in whites)MLS = 1.7(1273)
   BMI (in whites)MLS = 2.2 
  893 sibpairsBMI (in whites)p = 0.002, LOD = 1.95(1209)
      
D14S28314q11.2522 subjects, 99 families, 364 sibpairsFat mass (in whites)p = 0.0006(1273)
   Leptin (in whites)p = 0.003 
   Fat mass (in whites)MLS = 2 
   BMI (in whites)MLS = 1.8 
D14S128014q11.2522 subjects, 99 families, 364 sibpairsFat-free mass (in whites)MLS = 1.1(1273)
   BMI (in whites)MLS = 2.4 
D14S60814q121100 subjects, 170 familiesAdiponectin (in Northern Europeans)LOD = 3.2(1229)
D14S59914q13.11100 subjects, 170 familiesAdiponectin (in Northern Europeans)LOD = 3.2(1229)
D14S27614q22.2672 subjects, 28 pedigreesWaist circumference (in Old Order Amish)LOD = 1.8(1271)
D14S58814q24.1215 subjects, 105 familiesAbdominal subcutaneous fatLOD = 2.4(1237)
D14S7414q24.3672 subjects, 28 pedigreesLeptin (in Old Order Amish)LOD = 2.5(1271)
D14S28014q32.12672 subjects, 28 pedigreesLeptin (in Old Order Amish)LOD = 2.5(1271)
D14S61714q32.121055 pairsBMILOD = 2.2(1241)
D15S128-D15S51315q12-15q15.1506 subjects, 115 pedigreesAge adiposity reboundLOD = 2.53(1239)
D15S123215q13.33027 subjects, 401 families, 317 sibshipsBMI (National Heart, Lung, and Blood Institute Family Heart Study)LOD = 1.7(1220)
D15S64115q15.2478 subjects, 10 familiesasp levelsLOD = 2.1(1283)
   asp and high-density lipoprotein 2a-cholesterolLOD = 3.2 
LIPC15q21-23660 subjects, 202 families, 315 sibpairs, 274 men, 386 womenEating behavior, hungerLOD = 1.76(978)
D15S20615q24-q25660 subjects, 202 families, 315 sibpairs, 274 men, 386 womenEating behavior, hungerLOD = 3(978)
D15S65515q25.33383 subjects, 1124 familiesBody fat (%) (men)LOD = 3(1227)
D15S65215q26.1336 sibpairs, 609 relative pairsFat-free massLOD = 3.56(1263)
D15S65715q26.2336 sibpairs, 609 relative pairsFat-free massLOD = 2(1263)
D16S51016p13.3672 subjects, 28 pedigreesLeptin (in Old Order Amish)LOD = 1.7(1271)
   BMI (in Old Order Amish)LOD = 1.7 
D16S40416p13.2893 sibpairsBMI (in whites)p = 0.00025, LOD = 3.12(1209)
D16S76416p13.12893 sibpairsBMI (in whites)p = 0.0006, LOD = 2.45(1209)
D16S325316q12.2330 pedigrees, 1702 sibshipsBMILOD = 3.21(1261)
D16S415-D16S42016q12.2-16q24.1506 subjects, 115 pedigreesAge adiposity reboundLOD = 2.54(1239)
D16S262016q211055 pairsBMILOD = 2.6(1241)
D16S26516q211199 pairsLeptinLOD = 2(1260)
D16S42216q23.3995 subjects, 153 familiesResting energy expenditureLOD = 2.96(1284)
D17S849-D17S79917p13-17p13506 subjects, 115 pedigreesBMI > 95th percentileLOD = 2.25(1239)
D17S130817p13.3729 subjects, 275 familiesAbdominal subcutaneous fatMLS = 2.06(1210)
D17S130317p13.1478 subjects, 10 familiesasp levelsLOD = 2.7(1283)
D17S94717p121100 subjects, 170 familiesAdiponectin (in Northern Europeans)LOD = 1.7(1229)
  2209 subjects, 507 familiesLeptinLOD = 5(1248)
  1055 pairsBMILOD = 2.5(1241)
D17S129317q11.2470 subjects, 10 familiesBMIp = 0.001(1272)
D17S218017q21.32521 subjects, 156 familiesAbdominal subcutaneous fatLOD = 2.2(1219)
D17S130617q22660 subjects, 202 families, 315 sibpairs, 274 men, 386 womenEating behavior, hungerMLS = 2.06(978)
D17S129017q23.2660 subjects, 202 families, 315 sibpairs, 274 men, 386 womenEating behavior, hungerMLS = 2.45(978)
  729 subjects, 275 familiesBMIMLS = 2.76(1210)
  521 subjects, 156 familiesAbdominal subcutaneous fatLOD = 2.2(1219)
D17S94417q23.3-q25.1447 subjects, 109 pedigreesBMI > 35LOD = 3.16(1253)
D17S135117q23-q24660 subjects, 202 families, 315 sibpairs, 274 men, 386 womenEating behavior, hungerLOD = 1.75(978)
D17S130117q25.2521 subjects, 156 familiesAbdominal subcutaneous fatLOD = 2.2(1219)
D18S48118p11.3342 familiesTrends in BMI from childhood to adulthoodLOD = 2(1215)
D18S843-D18S5318p11.22- 18p11.233383 subjects, 1124 familiesBody fat (%) (men)LOD = 1.7(1227)
MC5R18p11.21289 pairsBMIp = 0.001(969)
   Skinfolds, sum of sixp = 0.005 
   Fat massp = 0.001 
   Body fat (%)p = 0.02 
   Fat-free massp = 0.008 
   Resting metabolic ratep = 0.002 
D18S87718q12.1336 sibpairs, 609 relative pairsFat-free massLOD = 3.6(1263)
  236 pairsBody fat (%) (in Pima Indians)LOD = 2.3(1214)
D18S53518q12.3336 sibpairs, 609 relative pairsFat-free massLOD = 3.58(1263)
D18S85818q21.313383 subjects, 1124 familiesBMI and blood pressure response to postural changeLOD = 2.6(1281)
D18S115518q21.32367 subjects, 166 families, 193 pairsObesity (in Finns)LOD = 2.4(1285)
MC4R18q22289 pairsRespiratory quotientp = 0.04(969)
D19S71419p13.3404 subjectsResistin mRNA levels in adipose tissue (adult baboons)LOD = 3.84(1286)
LDLR19p13.2522 subjects, 99 families, 364 sibpairsSkinfolds, sum of eight (in whites)p = 0.002(1273)
   Leptin (in whites)p = 0.0009 
   Body fat (%) (in whites)p = 0.009 
D19S221-D19S41419p13-19q13.11506 subjects, 115 pedigreesAge adiposity reboundLOD = 2.13(1239)
D19S21519p13660 subjects, 202 families, 315 sibpairs, 274 men, 386 womenEating behavior, disinhibitionLOD = 1.8(978)
D19S41819q13.3-q13.43447 subjects, 109 pedigreesBMI > 35LOD = 3.21(1253)
D19S41419q13.11369 subjects, 89 familiesObesity (in white children and adolescents)LOD = 1.97(1276)
D19S25419q13.43330 pedigrees, 1702 sibshipsObesity before age 35p = 0.001(1282)
D20S48220p13893 sibpairsBMI (in whites)p = 0.00016, LOD = 3.55(1209)
D20S85120p12.2893 sibpairsBMI (in whites)p = 4.6e−05, LOD = 4.08(1209)
  1724 subjects, 1202 familiesFactor central obesityMLS = 1.97(1247)
D20S60420p12.11724 subjects, 1202 familiesFactor central obesityMLS = 2.46(1247)
D20S60120q11.22-q11.23236 pairsRespiratory quotient, 24-hour (in Pima Indians)LOD = 3(1214)
D20S47820q12994 subjects, 37 pedigreesBMILOD = 2(1207)
D20S43820q121711 subjects, 103 pedigreesBMI (in Utah pedigrees)LOD = 3.5(1287)
  994 subjects, 37 pedigreesBMILOD = 2(1207)
D20S46520q12994 subjects, 37 pedigreesBMILOD = 2(1207)
D20S10720q12513 subjects, 92 families, 423 pairsBMILOD = 3.2(1288)
   Body fat (%)LOD = 3.2 
D20S47620q13513 subjects, 92 families, 423 pairsBMILOD = 3.06(1288)
ADA20q13.12160 pairsBMIp = 0.001(1252)
   skinfolds, sum of sixp = 0.001 
D20S48120q13.12994 subjects, 37 pedigreesBMILOD = 2.2(1207)
D20S1720q13.12650 subjects, 258 pairs, 152 pedigreesBody fat (%)p = 0.0078(662)
D20S17820q13.13667 subjects, 244 familiesBody fat (%) (in whites and African Americans)NPL = 2.57(1274)
D20S88720q13.13514 subjects, 99 families, 347 sibshipsFat intakep = 0.0093(1217)
D20S86920q13.13514 subjects, 99 families, 347 sibshipsCarbohydrate intakep = 0.0023(1217)
   Fat intakep = 0.0005 
   Protein intakep = 9e−05 
D20S85720q13.13514 subjects, 99 families, 347 sibshipsTotal energy intakep = 7e−05(1217)
   Carbohydrate intakep = 0.0008 
   Fat intakep = 0.0006 
   Protein intakep = 0.00022 
D20S83920q13.13514 subjects, 99 families, 347 sibshipsTotal energy intakep = 0.00014(1217)
   Carbohydrate intakep = 0.0009 
   Fat intakep = 0.0019 
   Protein intakep = 0.00041 
D20S48020q13.13514 subjects, 99 families, 347 sibshipsTotal energy intakep = 0.0003(1217)
   Carbohydrate intakep = 0.0006 
   Fat intakep = 0.0016 
   Protein intakep = 0.0009 
D20S21120q13.2513 subjects, 92 families, 423 pairsBMILOD = 3.2(1288)
  513 subjects, 92 families, 423 pairsBody fat (%)LOD = 3.2(1288)
D20S87620q13.13514 subjects, 99 families, 347 sibshipsTotal energy intakep = 0.00012(1217)
   Carbohydrate intakep = 0.001 
   Protein intakep = 0.00085 
D20S12020q13.2650 subjects, 258 pairs, 152 pedigreesBody fat (%)p = 0.004(662)
D20S14920q13.31-qter667 subjects, 244 familiesBody fat (%) (in whites and African Americans)NPL = 2.57(1274)
  513 subjects, 92 families, 423 pairsBMILOD = 3.2(1288)
   Body fat (%)LOD = 3.2 
D21S144221q21.23383 subjects, 1124 familiesBody fat (%) (women)LOD = 1.8(1227)
D21S205221q21.31510 subjects, 509 familiesFactor central obesityMLS = 2.13(1247)
D21S144021q22.121510 Subjects, 509 familiesFactor central obesityMLS = 2.13(1247)
D21S144621q22.31297 subjects, 260 familiesBody fat (%)LOD = 4.21(1226)
  1297 subjects, 260 familiesBody fat (%)LOD = 4.27(1246)
D22S26422q11.21453 subjects, 99 familiesAbdominal subcutaneous fatLOD = 1.96(1237)
D22S1685 (D20S608)22q11.21318 subjects, 10 familiesLeptinp = 0.001(1289)
A4GALT22q13.31>168 pairsBody weightp = 0.03(1208)
DXS8099Xp22.13994 subjects, 37 pedigreesBMILOD = 2.6(1207)
DXS997Xp21.31148 subjects, 133 families, 190 European-American families (940 members); 43 African-American families (208 members)Waist-to hip ratio (in European Americans and African Americans)LOD = 2.7(1290)
DXS1003Xp11.31148 subjects, 133 families, 190 European-American families (940 members); 43 African-American families (208 members)Waist-to-hip ratio (in European Americans and African Americans)LOD = 2.7(1290)
DXS1059Xq23994 subjects, 37 pedigreesBMILOD = 2(1207)
DXS6804Xq23367 subjects, 166 families, 193 pairsObesity (in Finns)LOD = 3.1(1285)
DXS1220Xq24184 families, 218 sibshipsObesityMLS = 1.93(1059)
AGTR25747C/TXq24184 families, 218 sibshipsObesityMLS = 2.3(1059)

Two genome scans for eating-related phenotypes were reported last year. The first was a genome scan for total caloric and macronutrient intakes assessed from a food frequency questionnaire in 816 subjects from the San Antonio Family Heart Study (1235). Evidence of linkage was found on chromosome 2p22-p21 near marker D2S1346 for total caloric intake and intakes of fat, saturated fat, and protein (LOD scores ranging from 2.09 to 2.62). The second was a genome scan of eating behaviors assessed from the Three-Factor Eating questionnaire in 660 subjects from the Quebec Family Study (978). Evidence of linkage was found on chromosomes 15q21-q23 (LIPC), 15q24-q25 (D15S206), and 17q22-q24 (D17S1306, D17S1290, D17S1351) for susceptibility to hunger and on chromosome 19p13 (D19S215) for disinhibition.

A genome-wide linkage analysis of obesity associated with the use of anti-psychotics in patients treated for psychoses was performed in 508 subjects from 21 multigenerational kindreds (1258). Obesity diagnosed from medical files was found to be 2.5 times more prevalent in patients treated with anti-psychotics than in untreated family members. Linkage with obesity and a set of 470 microsatellite markers was tested only in pedigrees with at least two occurrences of obesity. Evidence of linkage with obesity was found on chromosomes 6p23 (D6S260; LOD = 1.72), 8q22-q23 (D8S1136; LOD = 1.93), 9q34 (D9S282; LOD = 1.71), and 12q23.1-q24.23 (D12S1279-D12S366; LOD = 2.74).

Four genome scans reporting linkages with BMI and body fatness phenotype were published during the past year. In a study performed in West African families with type 2 diabetes (1236), linkage analysis of BMI and body composition assessed by bioelectric impedance revealed evidence of three QTLs affecting body fatness chromosomes 2p16-p13.3 (D2S2739-D2S441), 4q24 (D4S1647-D4S2623), and 5q14.3 (D5S1725). All linkages with BMI showed LOD scores below 1.7 (1236). A second genome scan for loci linked to BMI and percentage body fat assessed from bioelectric impedance was conducted in 3383 subjects from 1124 hypertensive African-American and white families (1227). Linkage to BMI and percentage body fat was tested separately in men and women and also in the combined sample. In the combined sample, evidence of linkage was found on chromosome 3q13.33 for BMI (LOD = 2.8) and on chromosome 12q24.3 for percentage body fat (LOD = 3.3). QTLs influencing both BMI and percentage body fat were found over a broad region [102 to 200 centimorgans (cM)] on chromosome 3 in men (3p12.2, 3q13.33, 3q26.33, and 3q27.3). Evidence of linkage with percentage body fat was also found on chromosomes 7q36.1 (LOD = 1.8), 15q25.3 (LOD = 3.0), and 18p11.22-p11.23 (LOD = 1.7) in men. In women, QTLs affecting percentage body fat were found on chromosomes 2p24.2 (LOD = 1.8), 12q24-q24.32 (LOD = 3.8), and 21q21.2 (LOD = 1.8), whereas linkage with BMI was found on chromosome 11p13 (LOD = 1.8). The third study was undertaken in a European-American sample of 1297 subjects from 260 families with the aim of detecting imprinted genetic loci influencing obesity-related traits (1224). Parent-specific linkage analyses of overweight (BMI ≥ 27), obesity (BMI ≥ 30), and obesity-related quantitative traits [BMI, percentage body fat, and waist circumference (WC)] were performed with 391 microsatellite markers. Several QTLs influencing obesity were uncovered: a paternal effect for BMI and WC on 2p25.1, a maternal effect for percentage body fat on 3p24, a paternal effect for BMI on 3q12.3, a maternal effect for obesity on 9q22.33, a maternal effect for overweight on 10p12.2, a paternal effect for percentage body fat on 11q12 and 11q13.3, a maternal effect for BMI and WC on 12q24.21, a maternal effect for overweight on 13q13.3, and a paternal effect for BMI and WC on 13q31.3. The fourth scan was undertaken in the same sample of European American families with the aim of detecting epistatic interactions among QTLs (1226). QTLs influencing BMI were found on chromosomes 2p24.2 and 4q28.3 and over a broad region of chromosome 13q21.1-q32.2, whereas QTLs influencing percentage body fat were found on chromosomes 12q24.21 and 21q22.3. Linkages with different obesity affection status (BMI ≥ 27, 30, 35, and 40) were found on chromosomes 3q12.3, 7q21.3, 7q22.1, 8q13.3, 9q22.33, 12p13.31, 12q23.1, 13q13.2, and 13q13.3. Significant evidence of interactions was found between loci on chromosome regions 2p25-p24 and 13q13-q21 (1226).

A search for genes influencing BMI, WHR, and abdominal fat assessed by computed tomography scan was undertaken in 330 subjects from 154 African-American families and in 729 subjects from 275 Hispanic-American families (1210). In the African-American families, significant linkage to BMI was found on chromosomes 1p36 (LOD = 2.14) and 3p26.3 (LOD = 3.67). In the Hispanic-American families, a QTL for BMI was found on chromosome 17q23.2 and QTLs for WHR were found on chromosomes 8q24.11, 12q13.13-q15, 12q21-q21.33, and 12q22-q24.21. QTLs for abdominal fat were found on chromosomes 5q33.2-q35.1, 8q11.22-q12.1, and 17p13.3 for abdominal subcutaneous fat and on chromosome 11q12.13-q13.3 for abdominal visceral fat. The last genome scan study was a genome-wide linkage analysis of four factors related to the metabolic syndrome derived from a factor analysis of 10 risk factors (1247). Factor analysis yielded four different metabolic syndrome factors (obesity-insulin, blood pressure, lipids-insulin, and central obesity) that were tested for linkage with 400 microsatellite markers in four different ethnic groups (blacks, whites, Hispanics, Asians). Only results with the central obesity factor are reported in Table 5. Evidence of linkage was found on chromosomes 13q31.3, 13q32.2, 20p12.2, and 20p12.1 in blacks, on chromosomes 11q13.3, 21q21.3, and 21q22.12 in whites, and on chromosomes 3q22.1, 5q35.2, 6p25.1, 6p23, and 8p23.3 in Asians. No evidence of linkage was found in Hispanics (1247).

A bivariate linkage analysis of metabolic syndrome phenotypes (BMI, WC, lipids, and insulin) with 19 markers located on chromosome 7q11.22-q22.1 performed in 440 subjects from 27 Mexican-American families revealed evidence of univariate linkage for BMI (LOD = 2.4) and WC (LOD = 2.0) between markers D7S653 and D7S479 and linkages (LOD scores ranging from 1.86 to 4.21) for most of the bivariate traits (BMI-lipids, BMI-insulin, WC-lipids, WC-insulin, BMI-WC) to a 6-cM region near marker D7S653 (1203).

Finally, a meta-analysis of genome scans that used BMI as their primary obesity phenotype and were published before July 2003 was undertaken to identify QTLs influencing obesity (1204). A total of 29 genome scans were identified from the literature; of these studies, 13 analyzed BMI as a quantitative trait. Access to detailed results was requested from the authors of the 13 studies, and information was obtained in only 5 of the 13 studies. The results from these five studies, which included a total of 2814 individuals from 505 families, were jointly analyzed using a variance component approach. For the purpose of the analysis, the genome was divided into 121 30-cM regions called bins in such a way that the first bin on chromosome 1 (1.1) includes the results of markers tested between locations 0 and 30 cM, the second bin (1.2) encompasses the 30- to 60-cM region of chromosome 1, and so on for all chromosomes. For each scan, the bins were then sorted according to the maximum LOD score in that bin, and ranks were assigned with the lowest rank assigned to the bin with the highest LOD score. Within each study, the ranks were weighted according to the number of genotyped individuals in the sample, and the weighted average rank was then calculated for each bin across the five studies. The bin with the lowest weighted average rank for all studies corresponded to the region of the genome showing the most evidence of linkage across all studies retained in the meta-analysis. The results of the analysis revealed that the lowest weighted average rank was found in bin 8.1, suggesting that the best evidence of linkage to BMI across all five studies is found at the location 0 to 30 cM on chromosome 8 (8pter-p23.3). Based on permutation testing, this was the only region showing significant (p = 0.0005) evidence of linkage to BMI. Interestingly, only two of the five studies retained in the meta-analysis showed suggestive evidence of linkage to BMI in that region of chromosome 8.

Conclusion

The 2005 human obesity gene map is depicted in Figure 1. The map includes >600 loci from single-gene mutations in mouse models of obesity, non-syndromic human obesity cases due to single-gene mutations, obesity-related Mendelian disorders that have been mapped, transgenic and KO mice models, QTLs from cross-breeding experiments and genome-wide scans, and genes or markers that have been shown to be associated or linked with an obesity phenotype. The map reveals that putative loci affecting obesity-related phenotypes are found on all chromosomes except Y. The number of genes and other markers associated or linked with human obesity phenotypes continues to increase, as indicated by the numbers collated in Table 6. Based on the various lines of evidence reviewed in the different sections of this report, there are now 135 different candidate genes that have been associated and/or linked with obesity-related phenotypes. The majority of the 127 candidate genes associated with obesity have been identified in association studies (Table 4). With the growing number of genes and loci indexed in the map, several genes and QTLs identified from association and genome scan studies have been replicated. We can now identify 22 different genes that have shown associations with obesity-related phenotypes in at least five studies. Among them, those showing replications in 10 studies and more include PPARG (30 studies), ADRB3 (29), ADRB2 (20), LEPR (16), GNB3 (14), UCP3 (12), ADIPOQ (11), LEP (11), UCP2 (11), HTR2C (10), NR3C1 (10), and UCP1 (10). The number of obesity QTLs identified from genome scans now reaches 253, which include 15 QTLs that have been replicated in at least three studies. The large number of genes and loci depicted in the obesity gene map is a good indication of the complexity of the task of identifying genes associated with the susceptibility to obesity. Although several of the genes listed in this report may be false positives, it is also clear that some genes are more important than others based on the numbers of replications from independent studies. A recent meta-analysis of genetic association studies concluded that, although false positive associations are abundant in the literature, 20% to 30% of genetic associations are real and have modest effects on risk of common diseases (1291). This would suggest that perhaps as many as 20 to 30 of the obesity candidate genes identified in this report might contribute to the risk of obesity in humans. Of course, the goal remains to identify the right combination of genes and mutations that are associated with this increased risk and to determine how environmental factors interact with these genes and mutations to determine the risk. We hope that the information provided in this publication will contribute in the years ahead to the resolution of this enormous challenge.

Figure 1.

The 2005 human obesity gene map. The map includes all obesity-related genes and QTLs identified from the various lines of evidence reviewed in this article. This year's map consists of a 862-band-resolution cytogenetic map overlaid with build 35.1 of the human genome sequence available from National Center for Biotechnology Information (http:www.ncbi.nlm.nih.gov). This allows the human genes (as abbreviated in the tables and appendix and located to the right of each chromosome in this figure) to be placed at precise positions on both the sequence and the cytogenetic map. For all loci, we used the name preferred by UniSTS or Entrez Gene. The ruler to the left of each figure represents kilobasepairs. Chromosomes are drawn to scale only within a given page and not on the last page. These maps, along with information from this report, can be browsed and searched interactively at the Obesity Gene Map web site (http:obesitygene.pbrc.edu).

Table 6.  Evolution in the status of the Human Obesity Gene Map
 199419951996199719981999200020012002200320042005
  • *

    Number of genes, not number of mutations.

Single-gene mutations*   2666666/71011
KO and Tg        3855166244
Mendelian disorders with map location81213161620242533414950
Animal QTLs7924556798115165168183221408
Human QTLs from genome scans   3814213368139204317
Candidate genes with positive findings9101321294048587190113127

Acknowledgement

This work was supported by the National Institutes of Health, the Canadian Institutes for Health Research, and the Pennington Biomedical Research Center. C.B. is supported by the George A. Bray Chair in Nutrition. We would like to recognize the contribution of Eric E. Snyder to earlier versions of this project and to its informatics system. We thank Nina Laidlaw for her help with development of the manuscript and the final version of the paper. The list of genes and markers currently in the map and the pictorial representation of the map and many other features are also available on the web site of the Pennington Biomedical Research Center, Human Genomics Laboratory at http:obesitygene.pbrc.edu

Footnotes

  • 1

    Nonstandard abbreviations: KO, knockout; QTL, quantitative trait locus; MC4R, melanocortin receptor 4; BDNF, brain-derived neurotrophic factor; NTRK2, neurotrophic tyrosine receptor kinase 2; AHO, Albright Hereditary Osteodystrophy; BW, body weight; MGI, Mouse Genome Informatics; LOD, logarithm of the odds ratio; WHR, waist-to-hip ratio; cM, centimorgan(s); WC, waist circumference.

Appendix. Symbols, full names, and cytogenetic location of genes and loci of the 2005 human obesity gene map

Gene or locusNameLocation (NCBI)
A4GALTα 1, 4-Galactosyltransferase (P1 blood group)22q13.31
ABCA7ATP-binding cassette, subfamily A, member 719p13.3
ABCC8ATP-binding cassette, subfamily C (CFTR/MRP), member 8 (sulfonylurea receptor)11p15.1
ABCG5ATP-binding cassette, subfamily G (WHITE), member 5 (sterolin 1)2p21
ACACBAcetyl-coenzyme A carboxylase β12q24.1
ACADVLAcyl-coenzyme A dehydrogenase, very long chain17p13-p11
ACEAngiotensin I-converting enzyme (peptidyl-dipeptidase A) 117q24.1
ACP1Acid phosphatase 1, soluble2p25
ADAAdenosine deaminase20q13.12
ADAM12ADAM metallopeptidase domain 12 (meltrin α)10q26.3
ADAMTS1A disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 121q21.2
ADCYAP1Adenylate cyclase-activating polypeptide 1 (pituitary)18p11
ADIPOQAdiponectin, C1Q, and collagen domain containing3q27
ADRA1BAdrenergic, α-1B-, receptor5q23-q32
ADRA2AAdrenergic, α-2A-, receptor10q24-q26
ADRA2BAdrenergic, α-2B-, receptor2q11.2
ADRB1Adrenergic, β-1-, receptor10q24-q26
ADRB2Adrenergic, β-2-, receptor, surface5q31-q32
ADRB3Adrenergic, β-3-, receptor8p12-p11.2
AEBP1AE-binding protein 17p13
AGPAT21-Acylglycerol-3-phosphate O-acyltransferase 2 (lysophosphatidic acid acyltransferase, β) (Bernardinelli-Seip congenital lipodystrophy 1)9q34.3
AGRPAgouti-related protein homolog (mouse)16q22
AGTAngiotensinogen (serine or cysteine) proteinase inhibitor, clade A (α-1 anti-proteinase, anti-trypsin; member 8)1q42.2
AGTR2Angiotensin II receptor, type 2Xq22-23
AHO2AHO 215q11-q13
AHSGα-2-HS-glycoprotein3q27
AK1Adenylate kinase 19q34.13
AKT1v-akt Murine thymoma viral oncogene homolog 114q32.3
AKT2v-akt Murine thymoma viral oncogene homolog 219q13.1-13.2
ALMS1Alstrom syndrome 12p13
ALPIAlkaline phosphatase, intestinal2q37.1
AMACRα-Methylacyl-coenzyme A racemase5p13.2-q11.1
ANGPTL4Angiopoietin-like 419p13.3
ANGPTL6Angiopoietin-like 619p13.2
ANMAAnisomastia (with obesity)16q13-q21
APOA1Apolipoprotein A-I11q23.3
APOA2Apolipoprotein A-II1q23.1
APOA4Apolipoprotein A-IV11q23.3
APOA5Apolipoprotein A-V11q23
APOBApolipoprotein B [including Ag(x) antigen]2p24.2
APOC1Apolipoprotein C-I19q13.2
APOC3Apolipoprotein C-III11q23.1-q23.2
APODApolipoprotein D3q26.2-qter
APOEApolipoprotein E19q13.32
AQP7Aquaporin 79p13
ARAndrogen receptor (dihydrotestosterone receptor, testicular feminization, spinal and bulbar muscular atrophy, Kennedy disease)Xq11.2-q12
ARID5BAT-rich interactive domain 5B (MRF1-like)10q21.2
ARL6ADP-ribosylation factor-like 63q11.2
ASIPAgouti signaling protein, non-agouti homolog (mouse)20q11.2-q12
ASPAAspartoacylase (Canavan disease)17pter-p13
ATP12AATPase, H+/K+ transporting, non-gastric, α polypeptide13q12.12
ATP1A2ATPase, Na+/K+ transporting, α2 (+) polypeptide1q23.1
ATP1B1ATPase, Na+/K+ transporting, β1 polypeptide1q23.3
ATP8B1ATPase, class I, type 8B, member 118q21-q22
BATFBasic leucine zipper transcription factor, ATF-like14q24.3
BBS1Bardet-Biedl syndrome 111q13.1
BBS2Bardet-Biedl syndrome 216q21
BBS3(ARL6)Bardet-Biedl syndrome 33p13-p12
BBS4Bardet-Biedl syndrome 4 (myosin IXA)15q22.3-23
BBS5Bardet-Biedl syndrome 52q31
BBS7Bardet-Biedl syndrome 74q27
BBS8(TTC8)Tetratricopeptide repeat domain 814q32.1
BDNFBDNF11p13
BFB-factor, properdin6p21.31
BRS3Bombesin-like receptor 3Xq26-q28
BSCL2Bernardinelli-Seip congenital lipodystrophy 2 (seipin)11q13
BUB1BBUB1 budding uninhibited by benzimidazoles 1 homolog β (yeast)15q15
C19orf20Chromosome 19 open reading frame 2019p13.3
C3Complement component 319p13.3
CAPN10Calpain 102q37.3
CARTCocaine- and amphetamine-regulated transcript5q13.2
CAV1Caveolin 17q31.1
CAV3Caveolin 33p25
CBFA2T1Core-binding factor, runt domain, α subunit 2; translocated to, 1; cyclin D-related8q21.3
CBLCas-Br-M (murine) ecotropic retroviral transforming sequence11q23.3
CCKARCholecystokinin A receptor4p15.1-15.2
CCKBRCholecystokinin B receptor11p15.4
CCND3Cyclin D36p21
CD36CD36 antigen (collagen type I receptor, thrombospondin receptor)7q11.2
CDH2Cadherin 2 (N-cadherin) (N-cadherin 1)18q11.2
CDKN1ACyclin-dependent kinase inhibitor 1A6p21.2
CDKN1Bp27Kip112p13.1-p12
CEBPACCAAT/enhancer-binding protein (C/EBP), α19q13.1
CEBPBC/EBP, β20q13.13
CEBPDC/EBP, Δ8p11.2-11.1
CHMChoroideremia (Rab escort protein 1)Xq21.2
CHRM3Cholinergic receptor, muscarinic 31q41-q44
CIDEACell death-inducing DFFA-like effector a18p11.21
CLOCKClock homolog (mouse)4q12
CNR1Cannabinoid receptor (brain)6q14-q15
CNTFRCiliary neurotrophic factor receptor9p13.2
COH1Cohen syndrome 18q22.2
COL8A2Collagen, type VIII, α21p34.3
COMTCatechol O-methyltransferase22q11.21
CORINCorin, serine peptidase4p13-12
CPECarboxypeptidase E4q32.3
CPT1ACarnitine palmitoyltransferase 1A (liver)11q13.1-13.2
CRHCorticotropin-releasing hormone8q13
CRHR1Corticotropin-releasing hormone receptor 117q12-q22
CRHR2Corticotropin-releasing hormone receptor 27p14.3
CYB5R4Cytochrome b5 reductase 46pter-q22.33
CYP11B2Cytochrome P450, family 11, subfamily B, polypeptide 28q21-q22
CYP19A1Cytochrome P450, family 19, subfamily A, polypeptide 115q21.1
CYP2D6Cytochrome P450, family 2, subfamily D, polypeptide 622q13.1
CYP7A1Cytochrome P450, family 7, subfamily A, polypeptide 18q12.1
DBHDopamine β-hydroxylase (dopamine β-monooxygenase)9q34
DFD component of complement (adipsin)19p13.3
DGAT1Diacylglycerol O-acyltransferase homolog 1 (mouse)8q24.3
DHCR2424-Dehydrocholesterol reductase1p33-31.1
DIO1Deiodinase, iodothyronine, type I1p33-p32
DLK1Δ-Like 1 homolog (Drosophila)14q32.3
DNAJC3DnaJ (Hsp40) homolog, subfamily C, member 313q32
DPTDermatopontin1q12-23
DRD2Dopamine receptor D211q23.2
DRD3Dopamine receptor D33q13.3
DRD4Dopamine receptor D411p15.5
EIF4EBP1Eukaryotic translation initiation factor 4E-binding protein 18p12
ENPP1Ectonucleotide pyrophosphatase/phosphodiesterase 16q23.1
EREGEpiregulin4q13.3
ESDEsterase D/formylglutathione hydrolase13q14.11
ESR1Estrogen receptor 16q25.1
ESR2Estrogen receptor 2 (ER β)14q23.2
ESRRAEstrogen-related receptor α11q13
FABP1Fatty acid-binding protein 1, liver2p11
FABP2Fatty acid-binding protein 2, intestinal4q27
FABP4Fatty acid-binding protein 4, adipocyte8q21
FABP5Fatty acid-binding protein 5 (psoriasis-associated)8q21.13
FASNFatty acid synthase17q25
FGF21Fibroblast growth factor 2119q31.1-qter
FGFR3Fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism)4p16.3
FKHL18Forkhead-like 18 (Drosophila)20q11.1-11.2
FMR1Fragile X mental retardation 1Xq28
FOSBFBJ murine osteosarcoma viral oncogene homolog B19q13.32
FOXA2Forkhead box A220p11
FOXC2Forkhead box C2 (MFH-1, mesenchyme forkhead 1)16q22-q24
FSHRFollicle-stimulating hormone receptor2p21
FXYD4FXYD domain containing ion transport regulator 410q11.21
GABRG3γ-Aminobutyric acid A receptor, γ315q11-q12
GAD2Glutamate decarboxylase 2 (pancreatic islets and brain, 65 kDa)10p11.23
GALGalanin11q13.2
GAMTGuanidinoacetate N-methyltransferase19p13.3
GAS6Growth arrestic-specific 613q34
GASTGastrin17q21
GCGRGlucagon receptor17q25
GCKGlucokinase (hexokinase 4, maturity onset diabetes of the young 2)7p15.3-p15.1
GDF3Growth differentiation factor 312p13.1
GDF8Growth differentiation factor 82q232.2
GFPT1Glutamine-fructose-6-phosphate transaminase 12p13
GFRA2GDNF family receptor α28p21
GH1Growth hormone (GH) 117q22-q24
GHRGH receptor5p13-12
GHRHGH-releasing hormone20q11.2
GHRHRGH-releasing hormone receptor7p14
GHRLGhrelin, GH secretagogue receptor ligand3p26-p25
GHSRGH secretagogue receptor3q26.31
GIPRGastric inhibitory polypeptide receptor19q13.3
GLO1Glyoxalase I6p21.3-p21.1
GNASGNAS complex locus20q13.2-q13.3
GNB3Guanine nucleotide-binding protein (G-protein), β polypeptide 312p13
GNG3Guanine nucleotide-binding protein (G-protein), γ311p11
GPAMGlycerol-3-phosphate acyltransferase, mitochondrial10q25.2
GPC1Glypican 12q35-q37
GPC3Glypican 3Xq26.2
GPC4Glypican 4Xq26.1
GPD2Glycerol-3-phosphate dehydrogenase 2 (mitochondrial)2q24.1
GPHB5Glycoprotein hormone β514q23.2
GPR10G-protein-coupled receptor 1010q26.13
GPR109AG-protein-coupled receptor 109A12q24.31
GPR24G-protein-coupled receptor 2422q13.3
GPR35G-protein-coupled receptor 352q37.3
GPR40G-protein-coupled receptor 4019q13.1
GPR7G-protein-coupled receptor 78p22-q21.13
GPX1Glutathione peroxidase 13p21.3
GRM5Glutamate receptor, metabotropic 511q14.3
GRM8Glutamate receptor, metabotropic 87 (q31.3-q32.1)
GSK3BGlycogen synthase kinase 3 β3q13.3
GYPAGlycophorin A (includes MN blood group)4q31.1
GYS1Glycogen synthase 1 (muscle)19q13.33
H6PDHexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase)1pter-p36.13
HCRTHypocretin (orexin) neuropeptide precursor17q21
HDHuntington (Huntington disease)4p16.3
HDCHistidine decarboxylase15q21-q22
HEXBHexosaminidase B (β polypeptide)5q13
HMGA2High-mobility group AT-hook 212q15
HRH1Histamine receptor H13p25
HRH3Histamine receptor H320q13.3
HSD11B1Hydroxysteroid (11-β) dehydrogenase 11q32-q41
HSD11B2Hydroxysteroid (11-β) dehydrogenase 216q22
HSD3B1Hydroxy-Δ-5-steroid dehydrogenase, 3 β- and steroid Δ-isomerase 11p11.2
HSPA1BHeat shock 70-kDa protein 1B6p21.31
HTR1B5-Hydroxytryptamine (serotonin) receptor 1B6q14.1
HTR2A5-Hydroxytryptamine (serotonin) receptor 2A13q14.11
HTR2C5-Hydroxytryptamine (serotonin) receptor 2CXq24
ICAM1Intercellular adhesion molecule 1 (CD54), human rhinovirus receptor19p13.2
IDEInsulin-degrading enzyme10q23-q25
IDH1Isocitrate dehydrogenase 1 (NADP+), soluble2q33.3
IFRD1Interferon-related developmental regulator 17q22-q31
IGF1Insulin-like growth factor 1 (somatomedin C)12q23.3
IGF2Insulin-like growth factor 2 (somatomedin A)11p15.5
IGFBP6Insulin-like growth factor-binding protein 612q13
IGKCImmunoglobulin kappa constant2p11.2
IL1RNInterleukin 1 receptor antagonist2q14.2
IL6Interleukin 6 (interferon, β2)7p21
IL6RInterleukin 6 receptor1q22
INPPL1Inositol polyphosphate phosphatase-like 111q23
INSInsulin11p15.5
INSRInsulin receptor19p13.3-p13.2
IPWImprinted in Prader-Willi syndrome15q11.2
IRS1Insulin receptor substrate 12q36.3
IRS2Insulin receptor substrate 213q34
ISL1ISL1 transcription factor, LIM/homeodomain, (islet-1)5q11.2
KCNA3Potassium voltage-gated channel, shaker-related subfamily, member 31p13.3
KCNJ11Potassium inwardly rectifying channel, subfamily J, member 1111p15.1
KELKell blood group7q35
KLF5Kruppel-like factor 5 (intestinal)13q22.1
LDLRLow-density lipoprotein receptor (familial hypercholesterolemia)19p13.2
LEPLeptin (obesity homolog, mouse)7q31.3
LEPRLeptin receptor1p31
LHBLuteinizing hormone β polypeptide19q13.32
LIPALipase A, lysosomal acid, cholesterol esterase (Wolfman disease)10q23.2-q23.3
LIPCLipase, hepatic15q21-23
LIPELipase, hormone-sensitive19q13.2
LMNALamin A/C1q23.1
LPIN1Lipin 12p25.1
LPLLipoprotein lipase8p21.3
LRPAP1Low-density lipoprotein receptor-related protein-associated protein 14p16.3
LTALymphotoxin α (TNF superfamily, member 1)6p21.3
MACS2SAH family member, acyl-coenzyme A synthetase for fatty acids16p12.3
MAGEL2MAGE-like 215q11.2
MAOAMonoamine oxidase AXp11.4-p11.3
MAPK3Mitogen-activated protein kinase 36p12-p11.2
MAPK8IP1Mitogen-activated protein kinase 8-interacting protein 111p11.2
MC3RMelanocortin 3 receptor20q13.2-q13.3
MC4RMelanocortin 4 receptor18q22
MC5RMelanocortin 5 receptor18p11.21
MECP2Methyl CpG-binding protein 2 (Rett syndrome)Xq28
MED12Trinucleotide repeat contain mediator of RNA polymerase II transcription, subunit 12 homolog (yeast)Xq13.1
MEHMOMental retardation, epileptic seizures, hypogonadism and -genitalism, microcephaly, and obesity syndromeXp22.13-p21.1
MEN1Multiple endocrine neoplasia I11q13
MESTMesoderm-specific transcript homolog (mouse)7q32
MKKSMcKusick-Kaufman syndrome20p12
MKRN3Makorin, ring finger protein, 315q11.2
MLXIPLMLX-interacting protein-like7q11.23
MMP11Matrix metallopeptidase 11 (stromelysin 3)22q11.23
MMP19Matrix metallopeptidase 1912q14
MRXS11Mental retardation, X-linked, syndromic 11Xq26-q27
MRXS7Mental retardation, X-linked, syndromic 7Xp11.3-q22.1
MT1AMetallothionein 1A (functional)16q13
MTTPMicrosomal triglyceride transfer protein4q24
MYCAvian myelocytomatosis viral (v-myc) oncogene homolog8q24.12-q24.13
NCB5ORNADPH cytochrome B5 oxidoreductase6pter-q22.33
NCOA3Nuclear receptor coactivator 320q13.13
NDNNecdin homolog (mouse)15q11.2
NHLH2Nescient helix loop helix 21p12-p11
NMBNeuromedin B15q22-qter
NMUNeuromedin U4q12
NOS2ANitric oxide synthase 2A (inducible, hepatocytes)17q11.2-12
NPBNeuropeptide B17q25.3
NPR3Natriuretic peptide receptor C/guanylate cyclase C (anti-natriuretic peptide receptor C)5p14-p13
NPYNeuropeptide Y7p15.1
NPY1RNeuropeptide Y receptor Y14q31.3-q32
NPY2RNeuropeptide Y receptor Y24q31
NPY5RNeuropeptide Y receptor Y54q31-q32
NR0B2Nuclear receptor subfamily 0, group B, member 21p35.3
NR1H2nuclear receptor subfamily 1, group H, member 219q13.3-13.2
NR1I3Nuclear receptor subfamily 1, group I, member 31q23.3
NR3C1Nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor)5q31
NTRK2Neurotrophic tyrosine kinase receptor type 29q22.1
NTSR1Neurotensin receptor 1 (high affinity)20q13-20q13
OPRM1Opioid receptor, μ16q24-q25
ORM1Orosomucoid 19q33.1
PAHPhenylalanine hydroxylase12q22-q24.2
PARP1Poly (ADP-ribose) polymerase family, member 11q41-q42
PAX6Paired box gene 6 (aniridia, keratitis)11p13
PCSK1Proprotein convertase subtilisin/kexin type 15q15-q21
PCSK1NProprotein convertase subtilisin/kexin type 1 inhibitorXp11.23
PEG3Paternally expressed 319q31.4
PEMTPhosphatidylethanolamine N-methyltransferase17p11.2
PGDPhosphogluconate dehydrogenase1p36.22
PGRProgesterone receptor11q22.2
PHF6PHD finger protein 6Xq26.3
PIK3R1Phosphoinositide-3-kinase, regulatory subunit 1 (p85 α)5q13.1
PIP5K2BPhosphatidylinositol-4-phosphate 5-kinase, type II, β17q12
PLA2G1BPhospholipase A2, group IB (pancreas)12q23-q24.1
PLINPerilipin15q26
PLSCR1Phospholipid scramblase 13q23
PLSCR3Phospholipid scramblase 317p13.1
PMCHPromelanin-concentrating hormone12q23-q24.1
PMM2Phosphomannomutase 216p13.2
PNMTPhenylethanolamine N-methyltransferase17q21.2
POMCproopiomelanocortin (adrenocorticotropin/β-lipotropin/α-melanocyte stimulating hormone/β-melanocyte stimulating hormone/β-endorphin)2p23.3
PON1Paraoxonase 17q21.3
PON2Paraoxonase 27q21.3
PORP450 (cytochrome) oxidoreductase7q11.2
PPARAPeroxisome proliferative-activated receptor, α22q13.31
PPARDPeroxisome proliferative-activated receptor, Δ6p21.2-p21.1
PPARGPeroxisome proliferative-activated receptor, γ3p25
PPARGC1APeroxisome proliferative-activated receptor, γ, coactivator 1 α4p15.1-15.2
PPARGC1BPeroxisome proliferative-activated receptor, γ, coactivator 1, β5q32
PPP1R3AProtein phosphatase 1, regulatory (inhibitor) subunit 3A (glycogen and sarcoplasmic reticulum-binding subunit, skeletal muscle)7q31.1
PPP1R3CProtein phosphatase 1, regulatory (inhibitor) subunit 3C10q23-q24
PPYPancreatic polypeptide17q21
PRKAA2Protein kinase, AMP-activated, α2 catalytic subunit1p31
PRKAG3AMP-aprotein kinase, AMP-activated, γ3 non-catalytic subunit2q35
PRKAR1Aprotein kinase, cAMP-dependent, regulatory, type I, α (tissue-specific extinguisher 1)17q24.3
PRKAR2BProtein kinase, cAMP-dependent, regulatory, type II, β7q22
PRKCQProtein kinase C, θ10p15
PRLHRProlactin-releasing hormone receptor10q26.13
PROP1Prophet of Pit1, paired-like homeodomain transcription factor5q35.3
PROX1Prospero-related homeobox 11q32.2-q32.3
PTPN1Protein tyrosine phosphatase, non-receptor type 120q13.1-q13.2
PTPN11Protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1)12q24
PTPNS1Protein tyrosine phosphatase, non-receptor type substrate 120p13
PTPRFProtein tyrosine phosphatase, receptor type, F1p34
PTTG1Pituitary tumor-transforming 15q35.1
PWCR1Prader-Willi syndrome critical region 115q11.2
PWLSXPrader-Willi-Like Syndrome, X-linkedXq23-q25
PYYPeptide YY17q21.1
RAI1Retinoic acid induced 117p11.2
RASGRF1Ras protein-specific guanine nucleotide-releasing factor 115q24
RENRenin1q32
RETNResistin (FIZZ3)19p13.2
RETNLBResistin-like β3q13.1
RPS6KA3Ribosomal protein S6 kinase, 90 kDa, polypeptide 3X p22.2-p22.1
RPS6KB1Ribosomal protein S6 kinase, 70 kDa, polypeptide 117q23.2
RSC1A1Regulatory solute carrier protein, family 1, member 11p36.1
RXRGRetinoid X receptor γ1q22-q23
SAHSA hypertension-associated homolog (rat)16p13.11
SCARB1Scavenger receptor class B, member 112q24.31
SCD1Stearyl-coenzyme A desaturase 110
SDC1Syndecan 12p24.1
SDC3Syndecan 3 (N-syndecan)1pter-p22.3
SERPINE1Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 17q21.3-q22
SFRP1Secreted frizzled-related protein 18p12-p11.1
SGBS2Simpson-Golabi-Behmel syndrome, type 2Xp22
SGKSerum/glucocorticoid regulated kinase6q23
SH2BSH2-B homolog16p11.2
SIM1Single-minded homolog 1 (Drosophila)6q16.3-q21
SLC2A2Solute carrier family 2 (facilitated glucose transporter), member 23q26.31
SLC2A4Solute carrier family 2 (facilitated glucose transporter), member 417p13
SLC6A1Solute carrier family 6 (neurotransmitter transporter, γ-aminobutyric acid), member 13p25-p24
SLC6A14Solute carrier family 6 (amino acid transporter), member 14Xq23-q24
SLC6A3Solute carrier family 6 (neurotransmitter transporter, dopamine), member 35p15.33
SNRPNSmall nuclear ribonucleoprotein polypeptide N15q12
SOAT2Sterol O-acyltransferase 212q13.13
SOCS3Suppressor of cytokine signaling 317q25.3
SORBS1Sorbin and SH3 domain containing 110q24.1
SOX8SRY (sex determining region Y)-box 816p13.3
SPARCSecreted protein, acidic, cysteine-rich (osteonectin)5q31.3-q32
SREBF1Sterol regulatory element-binding transcription factor 117p11.2
STAT3Signal transducer and activator of transcription 3 (acute-phase response factor)17q21.31
STAT5BSignal transducer and activator of transcription 5B17q11.2
STK25Serine/threonine kinase 25 (STE20 homolog, yeast)2q37.3
TBX3T-box 3 (ulnar mammary syndrome)12q24.21
TCF1Transcription factor 1, hepatic; LF-B1, hepatic nuclear factor (HNF1), albumin proximal factor12q24.31
TGFB1Transforming growth factor, β1 (Camurati-Engelmann disease)19q13.31
THTyrosine hydroxylase11p15.5
THRAThyroid hormone receptor, α [erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian]17q11.2
THRBThyroid hormone receptor, β [erythroblastic leukemia viral (v-erb-a) oncogene homolog 2, avian]3p24.1
TKTTransketolase (Wernicke-Korsakoff syndrome)3p14.3
TNFTNF (TNF superfamily, member 2)6p21.3
TNFRSF1BTNF receptor superfamily, member 1B1p36.21
TUBTubby homolog (mouse)11p15.5
TXNIPThioredoxin-interacting protein1q21.1
UBL5Ubiquitin-like 519p13.3
UBR1Ubiquitin protein ligase E3 component n-recognin 115q13
UCP1Uncoupling protein 1 (mitochondrial, proton carrier)4q28-q31
UCP2Uncoupling protein 2 (mitochondrial, proton carrier)11q13.3
UCP3Uncoupling protein 3 (mitochondrial, proton carrier)11q13
UNC5Cunc-5 homolog C (C. elegans)4q21-q23
VDRVitamin D (1, 25- dihydroxyvitamin D3) receptor12q13.11
VGFVGF nerve growth factor inducible7q22
VLDLRVery-low-density lipoprotein receptor9p24
VSX1Visual system homeobox 1 homolog, CHX10-like (zebrafish)20p11.21
WBSCR14Williams Beuren syndrome chromosome region 147q11.23
WNT10BWingless-type MMTV integration site family, member 10B12q13
WT1Wilms tumor 111p13
WTSWilson-Turner X-linked mental retardation syndromeXq21.2-q22
ZFP36Zinc finger protein 36, C3H type, homolog (mouse)19q13.1