Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder

被引：318

作者：

Neale, Benjamin M. ^{[1
,2
,3
]}

Medland, Sarah E. ^{[3
,4
]}

Ripke, Stephan ^{[1
,2
,3
]}

Asherson, Philip ^{[5
]}

Franke, Barbara ^{[6
]}

Lesch, Klaus-Peter ^{[13
]}

Faraone, Stephen V. ^{[7
]}

Nguyen, Thuy Trang ^{[8
]}

Schaefer, Helmut ^{[8
]}

Holmans, Peter ^{[9
]}

Daly, Mark ^{[1
,3
]}

Steinhausen, Hans-Christoph ^{[10
,11
,12
]}

Freitag, Christine ^{[14
]}

Reif, Andreas ^{[13
]}

Renner, Tobias J. ^{[13
]}

Romanos, Marcel ^{[13
]}

Romanos, Jasmin ^{[13
]}

Walitza, Susanne ^{[10
,13
]}

Warnke, Andreas ^{[13
]}

Meyer, Jobst ^{[15
]}

Palmason, Haukur ^{[15
]}

Buitelaar, Jan ^{[6
]}

Vasquez, Alejandro Arias ^{[6
]}

Lambregts-Rommelse, Nanda

Gill, Michael ^{[16
]}

Anney, Richard J. L. ^{[16
]}

Langely, Kate ^{[9
]}

O'Donovan, Michael ^{[17
]}

Williams, Nigel ^{[17
]}

Owen, Michael ^{[9
]}

Thapar, Anita ^{[9
]}

Kent, Lindsey ^{[18
]}

Sergeant, Joseph ^{[19
]}

Roeyers, Herbert ^{[20
]}

Mick, Eric ^{[19
,21
]}

Biederman, Joseph ^{[21
,22
]}

Doyle, Alysa ^{[18
,19
]}

Smalley, Susan ^{[23
]}

Loo, Sandra ^{[23
]}

Hakonarson, Hakon ^{[24
,25
]}

Elia, Josephine ^{[24
]}

Todorov, Alexandre ^{[26
]}

Miranda, Ana ^{[27
]}

Mulas, Fernando ^{[28
]}

Ebstein, Richard P. ^{[29
]}

Rothenberger, Aribert ^{[30
]}

Banaschewski, Tobias ^{[14
]}

Oades, Robert D. ^{[31
]}

Sonuga-Barke, Edmund J. S. ^{[5
,32
,33
]}

McGough, James ^{[23
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[2] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA

[3] MIT, Cambridge, MA 02139 USA

[4] Queensland Inst Med Res, Genet Epidemiol Unit, Brisbane, Qld 4006, Australia

[5] Kings Coll London, MRC Social Genet & Dev Psychiat, London, England

[6] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands

[7] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA

[8] Univ Marburg, Inst Med Biometrie & Epidemiol, Marburg, Germany

[9] MRC, Ctr Neuropsychiat Genet & Gen, Cardiff, S Glam, Wales

[10] Univ Zurich, Zurich, Switzerland

[11] Aarhus Univ Hosp, Aalborg Psychiat Hosp, Aarhus, Denmark

[12] Univ Basel, Inst Psychol, CH-4003 Basel, Switzerland

[13] Univ Wurzburg, Wurzburg, Germany

[14] Goethe Univ Frankfurt, Frankfurt, Germany

[15] Univ Trier, Inst Psychobiol, Trier, Germany

[16] St James Hosp, Trinity Ctr Hlth Sci, Dublin, Ireland

[17] Cardiff Univ, Sch Med, Cardiff, S Glam, Wales

[18] Bute Med Sch, St Andrews, Fife, Scotland

[19] Vrije Univ Amsterdam, Amsterdam, Netherlands

[20] Univ Ghent, B-9000 Ghent, Belgium

[21] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA

[22] Massachusetts Gen Hosp, Clin & Res Program, Pediat Psychopharmacol Adult ADHD, Boston, MA 02114 USA

[23] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA

[24] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[25] Univ Penn, Sch Med, Philadelphia, PA 19104 USA

[26] Washington Univ, Sch Med, St Louis, MO USA

[27] Univ Valencia, E-46003 Valencia, Spain

[28] La Fe Univ Hosp, Fac Med, Valencia, Spain

[29] Singapore & Hebrew Univ, Jerusalem, Israel

[30] Univ Gottingen, D-3400 Gottingen, Germany

[31] Univ Duisburg Essen, Clin Child & Adolescent Psychiat, Essen, Germany

[32] Univ Southampton, Sch Psychol, Inst Disorder Impulse & Attent, Southampton, NY USA

[33] NYU, Ctr Child Study, New York, NY USA

[34] Eli Lilly & Co, Indianapolis, IN 46285 USA

[35] Pfizer, Mol Med, Groton, CT USA

来源：

JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY | 2010年 / 49卷 / 09期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

ADHD; meta-analysis; association; GWAS; genetics; DEFICIT HYPERACTIVITY DISORDER; MOLECULAR-GENETICS; ADULT ADHD; SCAN; IDENTIFICATION; PREVALENCE; IMPUTATION; INFERENCE; LINKAGE; GENES;

D O I：

10.1016/j.jaac.2010.06.008

中图分类号：

B844 [发展心理学（人类心理学）];

学科分类号：

040202 ;

摘要：

Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of existing studies to boost statistical power. Method: We used data from four projects: a) the Children's Hospital of Philadelphia (CHOP); b) phase I of the International Multicenter ADHD Genetics project (IMAGE); c) phase II of IMAGE (IMAGE II); and d) the Pfizer-funded study from the University of California, Los Angeles, Washington University, and Massachusetts General Hospital (PUWMa). The final sample size consisted of 2,064 trios, 896 cases, and 2,455 controls. For each study, we imputed HapMap single nucleotide polymorphisms, computed association test statistics and transformed them to z-scores, and then combined weighted z-scores in a meta-analysis. Results: No genome-wide significant associations were found, although an analysis of candidate genes suggests that they may be involved in the disorder. Conclusions: Given that ADHD is a highly heritable disorder, our negative results suggest that the effects of common ADHD risk variants must, individually, be very small or that other types of variants, e.g., rare ones, account for much of the disorder's heritability. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(9):884-897.

引用

页码：884 / 897

页数：14

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