Genome-wide association study of inattention and hyperactivity-impulsivity measured as quantitative traits

Twin Res Hum Genet. 2013 Apr;16(2):560-74. doi: 10.1017/thg.2013.12.

Abstract

Genome-wide association studies (GWAS) of attention-deficit/hyperactivity disorder (ADHD) offer the benefit of a hypothesis-free approach to measuring the quantitative effect of genetic variants on affection status. Generally the findings of GWAS relying on ADHD status have been non-significant, but the one study using quantitative measures of symptoms found SLC9A9 and SLC6A1 were associated with inattention and hyperactivity-impulsivity. Accordingly, we performed a GWAS using quantitative measures of each ADHD subtype measured with the Strengths and Weaknesses of ADHD and Normal Behaviour (SWAN) scale in two community-based samples. This scale captures the full range of attention and kinetic behavior; from high levels of attention and appropriate activity to the inattention and hyperactivity-impulsivity associated with ADHD within two community-based samples. Our discovery sample comprised 1,851 participants (mean age = 22.8 years [4.8]; 50.6% female), while our replication sample comprised 155 participants (mean age = 26.3 years [3.1]; 68.4% females). Age, sex, age × sex, and age2 were included as covariates and the results from each sample were combined using meta-analysis, then analyzed with a gene-based test to estimate the combined effect of markers within genes. We compare our results with markers that have previously been found to have a strong association with ADHD symptoms. Neither the GWAS nor subsequent meta-analyses yielded genome-wide significant results; the strongest effect was observed at rs2110267 (4.62 × 10-7) for symptoms of hyperactivity-impulsivity. The strongest effect in the gene-based test was for GPR139 on symptoms of inattention (6.40 × 10-5). Replication of this study with larger samples will add to our understanding of the genetic etiology of ADHD.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Australia / epidemiology
  • Cohort Studies
  • Diseases in Twins / genetics*
  • Female
  • Genetics, Behavioral*
  • Genome-Wide Association Study*
  • Humans
  • Impulsive Behavior / genetics*
  • Male
  • Phenotype
  • Quantitative Trait, Heritable
  • Registries
  • Twins, Dizygotic / genetics*
  • Twins, Monozygotic / genetics*
  • Young Adult