Abbreviations: HW, Hardy-Weinberg; WC, Waist circumference; BMI, Body mass index.
Genome-wide linkage and regional association study of obesity-related phenotypes: The GenSalt study
Version of Record online: 2 JUL 2013
Copyright © 2013 The Obesity Society
Volume 22, Issue 2, pages 545–556, February 2014
How to Cite
Liu, A. Y., Gu, D., Hixson, J. E., Rao, D. C., Shimmin, L. C., Jaquish, C. E., Liu, D.-P., He, J. and Kelly, T. N. (2014), Genome-wide linkage and regional association study of obesity-related phenotypes: The GenSalt study. Obesity, 22: 545–556. doi: 10.1002/oby.20469
Funding agencies: The Genetic Epidemiology Network of Salt Sensitivity is supported by research grants (U01HL072507, R01HL087263, and R01HL090682) from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Disclosure: The authors have no conflicts of interest to disclose.
Author contributions: Study design: AY Liu, D Gu, JE Hixson, DC Rao, CE Jaquish, J He, TN Kelly. Phenotype collection: D Gu, D Liu, J He. Genotyping: JE Hixson, LC Shimmin. Data management: AY Liu, DC Rao, TN Kelly. Data analysis and interpretation: AY Liu, D Gu, JE Hixson, DC Rao, CE Jaquish, J He, TN Kelly. Manuscript preparation: AY Liu, J He, TN Kelly. Manuscript revision: AY Liu, D Gu, JE Hixson, DC Rao, CE Jaquish, J He, TN Kelly.
- Issue online: 3 FEB 2014
- Version of Record online: 2 JUL 2013
- Accepted manuscript online: 21 MAR 2013 11:41AM EST
- Manuscript Accepted: 11 MAR 2013
- Manuscript Received: 19 JAN 2012
To identify chromosomal regions harboring quantitative trait loci for waist circumference (WC) and body mass index (BMI).
Design and Methods
A genome-wide linkage scan and regional association study WC and BMI among 633 Chinese families was conducted.
A significant linkage signal for WC was observed at 22q13.31-22q13.33 in the overall analysis (LOD = 3.13). Follow-up association study of 22q13.31-13.33 revealed an association between the TBC1D22A gene marker rs16996195 and WC (false discovery rate [FDR]-Q < 0.05). In gender-stratified analysis, suggestive linkage signals were attained for WC at 2p24.3-2q12.2 and 22q13.33 among females (LOD = 2.54 and 2.15, respectively). Among males, 6q12-6q13 was suggestively linked to BMI (LOD = 2.03). Single marker association analyses at these regions identified male-specific relationships of six single nucleotide polymorphisms (SNPs) at 2p24.3-2q12.2 (rs100955, rs13020676, rs13014034, rs12990515, rs17024325, and rs2192712) and five SNPs at 6q12-6q13 (rs7747318, rs7767301, rs12197115, rs12203049, and rs9454847) with the obesity-related phenotypes (all FDR-Q < 0.05). At chromosome 6q12-6q13, markers rs7755450 and rs11758293 predicted BMI in females (both FDR-Q < 0.05).
Genomic regions on chromosomes 2, 6, and 22 which may harbor important obesity-susceptibility loci were described. Follow-up study of these regions revealed several novel variants associated with obesity related traits. Future work to confirm these promising findings is warranted.