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

Benjamin M. Neale, Sarah E. Medland, Stephan Ripke, Philip Asherson, Barbara Franke, Klaus Peter Lesch, Stephen V. Faraone, Thuy Trang Nguyen, Helmut Schäfer, Peter Holmans, Mark Daly, Hans Christoph Steinhausen, Christine Freitag, Andreas Reif, Tobias J. Renner, Marcel Romanos, Jasmin Romanos, Susanne Walitza, Andreas Warnke, Jobst MeyerHaukur Palmason, Jan Buitelaar, Alejandro Arias Vasquez, Nanda Lambregts-Rommelse, Michael Gill, Richard J.L. Anney, Kate Langely, Michael O'Donovan, Nigel Williams, Michael Owen, Anita Thapar, Lindsey Kent, Joseph Sergeant, Herbert Roeyers, Eric Mick, Joseph Biederman, Alysa Doyle, Susan Smalley, Sandra Loo, Hakon Hakonarson, Josephine Elia, Alexandre Todorov, Ana Miranda, Fernando Mulas, Richard P. Ebstein, Aribert Rothenberger, Tobias Banaschewski, Robert D. Oades, Edmund Sonuga-Barke, James McGough, Laura Nisenbaum, Frank Middleton, Xiaolan Hu, Stan Nelson

Research output: Contribution to journalArticlepeer-review

344 Scopus citations

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.

Original languageEnglish
Pages (from-to)884-897
Number of pages14
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume49
Issue number9
DOIs
StatePublished - Sep 2010
Externally publishedYes

Keywords

  • ADHD
  • GWAS
  • association
  • genetics
  • meta-analysis

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