Case-control genome-wide association study of attention-deficit/ hyperactivity disorder

Benjamin M Neale, Sarah E Medland, Stephan Ripke, Richard J Anney, Philip J Asherson, Jan K Buitelaar, Barbara Franke, Michael Gill, Lindsey S W Kent, Peter A Holmans, Frank A Middleton, Anita Thapar, Klaus Peter Lesch, Stephen V Faraone, Mark J Daly, Thuy Trang Nguyen, Helmut H Schafer, Hans Christoph Steinhausen, Andreas Reif, Tobias J RennerMarcel Romanos, Jasmin Romanos, Andreas Warnke, Susanne Walitza, Christine Margarete Freitag, Jobst D Meyer, Haukur Orvar Palmason, Aribert Rothenberger, Ziarih Hawi, Joseph A Sergeant, Herbert Roeyers, Eric O Mick, Joseph J Biederman

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127 Citations (Scopus)

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. Thus additional genomewide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases with DSM-IV ADHD genotyped using the Affymetrix 5.0 array and 2,455 repository controls screened for psychotic and bipolar symptoms genotyped using Affymetrix 6.0 arrays. A consensus SNP set was imputed using BEAGLE 3.0, resulting in an analysis dataset of 1,033,244 SNPs. Data were analyzed using a generalized linear model. Results: No genome-wide significant associations were found. The most significant results implicated the following genes: PRKG1, FLNC, TCERG1L, PPM1H, NXPH1, PPM1H, CDH13, HK1, and HKDC1. Conclusions: The current analyses are a useful addition to the present literature and will make a valuable contribution to future meta-analyses. The candidate gene findings are consistent with a prior meta-analysis in suggesting that the effects of ADHD risk variants must, individually, be very small and/or include multiple rare alleles
Original languageEnglish
Pages (from-to)906 - 920
Number of pages15
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume49
Issue number9
DOIs
Publication statusPublished - 2010
Externally publishedYes

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