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Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder.


ABSTRACT: 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.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.No genome-wide significant associations were found, although an analysis of candidate genes suggests that they may be involved in the disorder.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.

SUBMITTER: Neale BM 

PROVIDER: S-EPMC2928252 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder.

Neale Benjamin M BM   Medland Sarah E SE   Ripke Stephan S   Asherson Philip P   Franke Barbara B   Lesch Klaus-Peter KP   Faraone Stephen V SV   Nguyen Thuy Trang TT   Schäfer Helmut H   Holmans Peter P   Daly Mark M   Steinhausen Hans-Christoph HC   Freitag Christine C   Reif Andreas A   Renner Tobias J TJ   Romanos Marcel M   Romanos Jasmin J   Walitza Susanne S   Warnke Andreas A   Meyer Jobst J   Palmason Haukur H   Buitelaar Jan J   Vasquez Alejandro Arias AA   Lambregts-Rommelse Nanda N   Gill Michael M   Anney Richard J L RJ   Langely Kate K   O'Donovan Michael M   Williams Nigel N   Owen Michael M   Thapar Anita A   Kent Lindsey L   Sergeant Joseph J   Roeyers Herbert H   Mick Eric E   Biederman Joseph J   Doyle Alysa A   Smalley Susan S   Loo Sandra S   Hakonarson Hakon H   Elia Josephine J   Todorov Alexandre A   Miranda Ana A   Mulas Fernando F   Ebstein Richard P RP   Rothenberger Aribert A   Banaschewski Tobias T   Oades Robert D RD   Sonuga-Barke Edmund E   McGough James J   Nisenbaum Laura L   Middleton Frank F   Hu Xiaolan X   Nelson Stan S  

Journal of the American Academy of Child and Adolescent Psychiatry 20100801 9


<h4>Objective</h4>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.<h4>Method</h4>We used data from four projects: a) the Children's Hospital of Philadelphia (CHOP); b) p  ...[more]

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