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

Neale, Benjamin M., Medland, Sarah E., Ripke, Stephan, Asherson, Philip, Franke, Barbara, Lesch, Klaus-Peter, Faraone, Stephen V., Nguyen, Thuy Trang, Schäfer, Helmut, Holmans, Peter Alan ORCID:, Daly, Mark, Steinhausen, Hans-Christoph, Freitag, Christine, Reif, Andreas, Renner, Tobias J., Romanos, Marcel, Romanos, Jasmin, Walitza, Susanne, Warnke, Andreas, Meyer, Jobst, Palmason, Haukur, Buitelaar, Jan, Vasquez, Alejandro Arias, Lambregts-Rommelse, Nanda, Gill, Michael, Anney, Richard ORCID:, Langley, Kate ORCID:, O'Donovan, Michael Conlon ORCID:, Williams, Nigel Melville ORCID:, Owen, Michael John ORCID:, Thapar, Anita ORCID:, Kent, Lindsey, Sergeant, Joseph, Roeyers, Herbert, Mick, Eric, Biederman, Joseph, Doyle, Alysa, Smalley, Susan, Loo, Sandra, Hakonarson, Hakon, Elia, Josephine, Todorov, Alexandre, Ana, Miranda, Mulas, Fernando, Ebstein, Richard P., Rothenberger, Aribert, Banaschewski, Tobias, Oades, Richard D., Sonuga-Barke, Edmund, McGough, James, Nisenbaum, Laura, Middleton, Frank, Hu, Xiaolan and Nelson, Stan 2010. Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder. Journal of the American Academy of Child & Adolescent Psychiatry 49 (9) , pp. 884-897. 10.1016/j.jaac.2010.06.008

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Uncontrolled Keywords: ADHD, meta-analysis, association, GWAS, genetics
Publisher: Elsevier
ISSN: 0890-8567
Last Modified: 06 Dec 2022 09:45

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