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

J Am Acad Child Adolesc Psychiatry. 2010 Sep;49(9):906-20. doi: 10.1016/j.jaac.2010.06.007. Epub 2010 Aug 5.

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Case-Control Studies
  • Child
  • Comorbidity
  • Diseases in Twins / diagnosis
  • Diseases in Twins / genetics
  • Diseases in Twins / psychology
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics