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


Neale, B M; et al; Steinhausen, H C; Langely, K; Psych, F R C; Thapar, A; Hu, X (2010). Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 49(9):884-897.

Abstract

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.
2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

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.
2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Citations

146 citations in Web of Science®
158 citations in Scopus®
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Additional indexing

Contributors:Psychiatric GWAS Consortium: ADHD Subgroup
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:17 Jan 2011 17:44
Last Modified:05 Apr 2016 14:33
Publisher:Elsevier
ISSN:0890-8567
Publisher DOI:10.1016/j.jaac.2010.06.008
PubMed ID:20732625

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