title: Genome-wide association study of inattention and hyperactivity-impulsivity measured as quantitative traits.
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.
authors.affiliation: School of Environmental and Rural Sciences, University of New England, Armidale, New South Wales, Australia. jebejer@une.edu.au
authors.forename: Jane L
authors.initials: JL
authors.lastname: Ebejer
authors.forename: David L
authors.initials: DL
authors.lastname: Duffy
authors.forename: Julius
authors.initials: J
authors.lastname: van der Werf
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.forename: Grant
authors.initials: G
authors.lastname: Montgomery
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Gillespie
authors.forename: Ian B
authors.initials: IB
authors.lastname: Hickie
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Medland
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology; D001315:Australia / Q000453:epidemiology; D015331:Cohort Studies; D004200:Diseases in Twins / Q000235:genetics*; D005260:Female; D005824:Genetics, Behavioral; D055106:Genome-Wide Association Study; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics*; D008297:Male; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D012042:Registries; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*; D055815:Young Adult