Case-Control Genome-Wide Association Study of Attention-Deficit/Hyperactivity Disorder

Benjamin M. Neale, Sarah Medland, Stephan Ripke, Richard J. L. Anney, Philip Asherson, Jan Buitelaar, Barbara Franke, Michael Gill, Lindsey Kent, Peter Holmans, Frank Middleton, Anita Thapar, Klaus-Peter Lesch, Stephen V. Faraone, Mark Daly, Thuy Trang Nguyen, Helmut Schaefer, Hans-Christoph Steinhausen, Andreas Reif, Tobias J. RennerMarcel Romanos, Jasmin Romanos, Andreas Warnke, Susanne Walitza, Christine Freitag, Jobst Meyer, Haukur Palmason, Aribert Rothenberger, Ziarih Hawi, Joseph Sergeant, Herbert Roeyers, Eric Mick, Joseph Biederman, IMAGE II Consortium

Research output: Contribution to journalArticlepeer-review

130 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 genotvped 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 genomewide 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. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(9):906-920.

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 - Sept 2010

Keywords

  • ADHD
  • genetics
  • genome-wide association
  • imputation
  • DEFICIT HYPERACTIVITY DISORDER
  • PROTEIN-KINASE-I
  • INTERNATIONAL HAPMAP PROJECT
  • SUBSTANCE USE DISORDERS
  • LONG-TERM POTENTIATION
  • MOLECULAR-GENETICS
  • SUSCEPTIBILITY LOCI
  • BIPOLAR DISORDER
  • COMMON VARIANTS
  • CANDIDATE GENES

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