Common obesity risk alleles in childhood attention-deficit/hyperactivity disorder

Authors

  • Özgür Albayrak,

    Corresponding author
    1. Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, LVR Klinikum Essen, University of Duisburg-Essen, Germany
    • Department of Child and Adolescent Psychiatry Psychotherapy and Psychosomatics, LVR Klinikum Essen, University of Duisburg-Essen, Wickenburgstr. 21, D-45147 Essen, Germany.
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  • Carolin Pütter,

    1. Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Germany
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  • Anna-Lena Volckmar,

    1. Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, LVR Klinikum Essen, University of Duisburg-Essen, Germany
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  • Sven Cichon,

    1. Institute of Neuroscience and Medicine (INM-1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Center Jülich, Juelich, Germany
    2. Institute of Human Genetics, University of Bonn, Germany
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  • Per Hoffmann,

    1. Institute of Human Genetics, University of Bonn, Germany
    2. Department of Genomics, Life & Brain Center, University of Bonn, Germany
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  • Markus M. Nöthen,

    1. Institute of Human Genetics, University of Bonn, Germany
    2. Department of Genomics, Life & Brain Center, University of Bonn, Germany
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  • Karl-Heinz Jöckel,

    1. Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Germany
    2. For the Heinz Nixdorf Recall Study Group
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  • Stefan Schreiber,

    1. For the Popgen Study Group, Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Germany
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  • H-Erich Wichmann,

    1. For the KORA Study Group, Institute of Epidemiologyl, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany
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  • Stephen V. Faraone,

    1. Medical Genetics Research, Child and Adolescent Psychiatry Research SUNY Upstate Medical University, Syracuse, New York, USA
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    • Collaborators of the Psychiatric GWAS Consortium: ADHD subgroup: Hans-Christoph Steinhausen (Aalborg, Denmark & Basel, and Zurich, Switzerland); Klaus-Peter Lesch, Andreas Reif, Tobias J. Renner, Marcel Romanos, Jasmin Romanos, SusanneWalitza, AndreasWarnke, ThuyTrang Nguyen, Helmut Schäfer (Würzburg and Marburg, Germany), Christine Freitag, Jobst Meyer, Haukur Palmason (Frankfurt/Homburg and Trier, Germany), Jan Buitelaar (Radboud University Nijmegen Medical Center, Donders Institute for Brain Cognition and Behavior, Nijmegen, Netherlands), Barbara Franke, Alejandro Arias Vasquez (Nijmegen/Utrecht, The Netherlands), Michael Gill, Richard J.L. Anney (Dublin, Ireland), Kate Langley, Michael O'Donovan, Nigel Williams, Peter Holmans, Michael Owen, Anita Thapar (Cardiff, Wales, UK), Lindsey Kent (St. Andrews, Scotland, UK), Joseph Sergeant (Amsterdam, The Netherlands), Herbert Roeyers (Gent, Belgium), Philip Asherson (London, UK), Eric Mick, Alysa Doyle, Joseph Biederman, (Boston, USA), Susan Smalley, Sandra Loo (Los Angeles, USA), Hakon Hakonarson, Josephine Elia (Philadelphia, USA), Alexandre Todorov (St. Louis, USA), Ana Miranda (Valencia, Spain), Richard Ebstein (Jerusalem, Israel), Aribert Rothenberger, Tobias Banaschewski (Mannheim/Goettingen, Germany), Robert Oades (Essen, Germany), James McGough (Los Angeles, USA), Frank Middleton (SUNY Upstate Medical University, Syracuse, NY), Xiaolan Hu (Pfizer, Groton, CT), Stan Nelson (UCLA, Los Angeles, CA), Benjamin M Neale (Boston, MA), Stephen V. Faraone (SUNY Upstate Medical University, Syracuse, NY, Chair). grant sponsor: German Research Association (DFG); grant numbers: He1446/9-1, KFO 125, SFB 581, GRK 1156, ME 1923/5-1, ME 1923/5-3, GRK 1389, SCHA 542/10-3; grant sponsor: Bundesministerium für Bildung und Forschung; grant number: BMBF 01GV0605; grant sponsor: US National of Institute of Health; Grant numbers: R13MH059126, R01MH62873, R01MH081803, K23MH066275, MH58277; grant sponsor: University of Pennsylvania CTR; grant number: UL1-RR-024134; grant sponsor: Institutional Development Award to the Center for Applied Genomics from the Children's Hospital of Philadelphia; grant sponsor: Affymetrix Power Award, 2007; grant sponsor: NHMRC (Australia); grant number: 443036; grant sponsor: Sidney Sax Public Health Fellowship; grant number: 443036; grant sponsor: Wellcome Trust, UK for sample; grant sponsor: UMC Utrecht Genvlag Grant; grant sponsor: Internal Grant of Radboud University Nijmegen Medical Centre.

  • Benjamin M. Neale,

    1. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
    2. Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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    • Collaborators of the Psychiatric GWAS Consortium: ADHD subgroup: Hans-Christoph Steinhausen (Aalborg, Denmark & Basel, and Zurich, Switzerland); Klaus-Peter Lesch, Andreas Reif, Tobias J. Renner, Marcel Romanos, Jasmin Romanos, SusanneWalitza, AndreasWarnke, ThuyTrang Nguyen, Helmut Schäfer (Würzburg and Marburg, Germany), Christine Freitag, Jobst Meyer, Haukur Palmason (Frankfurt/Homburg and Trier, Germany), Jan Buitelaar (Radboud University Nijmegen Medical Center, Donders Institute for Brain Cognition and Behavior, Nijmegen, Netherlands), Barbara Franke, Alejandro Arias Vasquez (Nijmegen/Utrecht, The Netherlands), Michael Gill, Richard J.L. Anney (Dublin, Ireland), Kate Langley, Michael O'Donovan, Nigel Williams, Peter Holmans, Michael Owen, Anita Thapar (Cardiff, Wales, UK), Lindsey Kent (St. Andrews, Scotland, UK), Joseph Sergeant (Amsterdam, The Netherlands), Herbert Roeyers (Gent, Belgium), Philip Asherson (London, UK), Eric Mick, Alysa Doyle, Joseph Biederman, (Boston, USA), Susan Smalley, Sandra Loo (Los Angeles, USA), Hakon Hakonarson, Josephine Elia (Philadelphia, USA), Alexandre Todorov (St. Louis, USA), Ana Miranda (Valencia, Spain), Richard Ebstein (Jerusalem, Israel), Aribert Rothenberger, Tobias Banaschewski (Mannheim/Goettingen, Germany), Robert Oades (Essen, Germany), James McGough (Los Angeles, USA), Frank Middleton (SUNY Upstate Medical University, Syracuse, NY), Xiaolan Hu (Pfizer, Groton, CT), Stan Nelson (UCLA, Los Angeles, CA), Benjamin M Neale (Boston, MA), Stephen V. Faraone (SUNY Upstate Medical University, Syracuse, NY, Chair). grant sponsor: German Research Association (DFG); grant numbers: He1446/9-1, KFO 125, SFB 581, GRK 1156, ME 1923/5-1, ME 1923/5-3, GRK 1389, SCHA 542/10-3; grant sponsor: Bundesministerium für Bildung und Forschung; grant number: BMBF 01GV0605; grant sponsor: US National of Institute of Health; Grant numbers: R13MH059126, R01MH62873, R01MH081803, K23MH066275, MH58277; grant sponsor: University of Pennsylvania CTR; grant number: UL1-RR-024134; grant sponsor: Institutional Development Award to the Center for Applied Genomics from the Children's Hospital of Philadelphia; grant sponsor: Affymetrix Power Award, 2007; grant sponsor: NHMRC (Australia); grant number: 443036; grant sponsor: Sidney Sax Public Health Fellowship; grant number: 443036; grant sponsor: Wellcome Trust, UK for sample; grant sponsor: UMC Utrecht Genvlag Grant; grant sponsor: Internal Grant of Radboud University Nijmegen Medical Centre.

  • Beate Herpertz-Dahlmann,

    1. Department of Child and Adolescent Psychiatry, Technical University of Aachen, Germany
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  • Gerd Lehmkuhl,

    1. Department of Child and Adolescent Psychiatry, University of Cologne, Germany
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  • Judith Sinzig,

    1. Department of Child and Adolescent Psychiatry, University of Cologne, Germany
    2. Department for Child and Adolescent Psychiatry and Psychotherapy, LVR Linikum Bonn, Germany
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  • Tobias J. Renner,

    1. Department of Child and Adolescent Psychiatry, Julius-Maximilians, University of Würzburg, Germany
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  • Marcel Romanos,

    1. Department of Child and Adolescent Psychiatry, Julius-Maximilians, University of Würzburg, Germany
    2. Department of Child and Adolescent Psychiatry, University of Munich, Germany
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  • Andreas Warnke,

    1. Department of Child and Adolescent Psychiatry, Julius-Maximilians, University of Würzburg, Germany
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  • Klaus-Peter Lesch,

    1. Department of Psychiatry and Psychotherapy, Julius-Maximilians, University of Würzburg, Germany
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  • Andreas Reif,

    1. Department of Psychiatry and Psychotherapy, Julius-Maximilians, University of Würzburg, Germany
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  • Benno G. Schimmelmann,

    1. University Hospital of Child and Adolescent Psychiatry, University of Bern, Switzerland
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  • André Scherag,

    1. Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Germany
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  • Johannes Hebebrand,

    1. Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, LVR Klinikum Essen, University of Duisburg-Essen, Germany
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  • Anke Hinney,

    1. Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, LVR Klinikum Essen, University of Duisburg-Essen, Germany
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  • Psychiatric GWAS Consortium: ADHD Subgroup

    Search for more papers by this author
    • Collaborators of the Psychiatric GWAS Consortium: ADHD subgroup: Hans-Christoph Steinhausen (Aalborg, Denmark & Basel, and Zurich, Switzerland); Klaus-Peter Lesch, Andreas Reif, Tobias J. Renner, Marcel Romanos, Jasmin Romanos, SusanneWalitza, AndreasWarnke, ThuyTrang Nguyen, Helmut Schäfer (Würzburg and Marburg, Germany), Christine Freitag, Jobst Meyer, Haukur Palmason (Frankfurt/Homburg and Trier, Germany), Jan Buitelaar (Radboud University Nijmegen Medical Center, Donders Institute for Brain Cognition and Behavior, Nijmegen, Netherlands), Barbara Franke, Alejandro Arias Vasquez (Nijmegen/Utrecht, The Netherlands), Michael Gill, Richard J.L. Anney (Dublin, Ireland), Kate Langley, Michael O'Donovan, Nigel Williams, Peter Holmans, Michael Owen, Anita Thapar (Cardiff, Wales, UK), Lindsey Kent (St. Andrews, Scotland, UK), Joseph Sergeant (Amsterdam, The Netherlands), Herbert Roeyers (Gent, Belgium), Philip Asherson (London, UK), Eric Mick, Alysa Doyle, Joseph Biederman, (Boston, USA), Susan Smalley, Sandra Loo (Los Angeles, USA), Hakon Hakonarson, Josephine Elia (Philadelphia, USA), Alexandre Todorov (St. Louis, USA), Ana Miranda (Valencia, Spain), Richard Ebstein (Jerusalem, Israel), Aribert Rothenberger, Tobias Banaschewski (Mannheim/Goettingen, Germany), Robert Oades (Essen, Germany), James McGough (Los Angeles, USA), Frank Middleton (SUNY Upstate Medical University, Syracuse, NY), Xiaolan Hu (Pfizer, Groton, CT), Stan Nelson (UCLA, Los Angeles, CA), Benjamin M Neale (Boston, MA), Stephen V. Faraone (SUNY Upstate Medical University, Syracuse, NY, Chair). grant sponsor: German Research Association (DFG); grant numbers: He1446/9-1, KFO 125, SFB 581, GRK 1156, ME 1923/5-1, ME 1923/5-3, GRK 1389, SCHA 542/10-3; grant sponsor: Bundesministerium für Bildung und Forschung; grant number: BMBF 01GV0605; grant sponsor: US National of Institute of Health; Grant numbers: R13MH059126, R01MH62873, R01MH081803, K23MH066275, MH58277; grant sponsor: University of Pennsylvania CTR; grant number: UL1-RR-024134; grant sponsor: Institutional Development Award to the Center for Applied Genomics from the Children's Hospital of Philadelphia; grant sponsor: Affymetrix Power Award, 2007; grant sponsor: NHMRC (Australia); grant number: 443036; grant sponsor: Sidney Sax Public Health Fellowship; grant number: 443036; grant sponsor: Wellcome Trust, UK for sample; grant sponsor: UMC Utrecht Genvlag Grant; grant sponsor: Internal Grant of Radboud University Nijmegen Medical Centre.


  • How to Cite this Article: Albayrak, Z, Pütter C, Volckmar A-L, Cichon S, Hoffmann P, Nöthen MM, Jöckel K-H, Schreiber S, Wichmann H-E, Faraone SV, Neale BM, Herpertz-Dahlmann B, Lehmkuhl G, Sinzig J, Renner TJ, Romanos M, Warnke A, Lesch K-P, Reif A, Schimmelmann BG, Scherag A, Hebebrand J, Hinney A, Psychiatric GWAS Consortium: ADHD Subgroup. 2013. Common Obesity Risk Alleles in Childhood Attention-Deficit/Hyperactivity Disorder. Am J Med Genet Part B 162B:295–305.

Abstract

Children with attention-deficit/hyperactivity disorder (ADHD) have a higher rate of obesity than children without ADHD. Obesity risk alleles may overlap with those relevant for ADHD. We examined whether risk alleles for an increased body mass index (BMI) are associated with ADHD and related quantitative traits (inattention and hyperactivity/impulsivity). We screened 32 obesity risk alleles of single nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) for ADHD based on 495 patients and 1,300 population-based controls and performed in silico analyses of the SNPs in an ADHD meta-analysis comprising 2,064 trios, 896 independent cases, and 2,455 controls. In the German sample rs206936 in the NUDT3 gene (nudix; nucleoside diphosphate linked moiety X-type motif 3) was associated with ADHD risk (OR: 1.39; P = 3.4 × 10−4; Pcorr = 0.01). In the meta-analysis data we found rs6497416 in the intronic region of the GPRC5B gene (G protein-coupled receptor, family C, group 5, member B; P = 7.2 × 10−4; Pcorr = 0.02) as a risk allele for ADHD. GPRC5B belongs to the metabotropic glutamate receptor family, which has been implicated in the etiology of ADHD. In the German sample rs206936 (NUDT3) and rs10938397 in the glucosamine-6-phosphate deaminase 2 gene (GNPDA2) were associated with inattention, whereas markers in the mitogen-activated protein kinase 5 gene (MAP2K5) and in the cell adhesion molecule 2 gene (CADM2) were associated with hyperactivity. In the meta-analysis data, MAP2K5 was associated with inattention, GPRC5B with hyperactivity/impulsivity and inattention and CADM2 with hyperactivity/impulsivity. Our results justify further research on the elucidation of the common genetic background of ADHD and obesity. © 2013 Wiley Periodicals, Inc.

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