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Genome-Wide Association Study of Inattention and Hyperactivity–Impulsivity Measured as Quantitative Traits

  • Jane L. Ebejer (a1) (a2), David L. Duffy (a2), Julius van der Werf (a1), Margaret J. Wright (a2), Grant Montgomery (a2), Nathan A. Gillespie (a2) (a3), Ian B. Hickie (a4), Nicholas G. Martin (a2) and Sarah E. Medland (a2)...

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.

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Copyright

Corresponding author

Address for correspondence: Jane Ebejer, Genetic Epidemiology Unit, Queensland Institute of Medical Research, 300 Herston Rd, Brisbane QLD 4006, Australia. E-mail: jebejer@une.edu.au

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Keywords

Genome-Wide Association Study of Inattention and Hyperactivity–Impulsivity Measured as Quantitative Traits

  • Jane L. Ebejer (a1) (a2), David L. Duffy (a2), Julius van der Werf (a1), Margaret J. Wright (a2), Grant Montgomery (a2), Nathan A. Gillespie (a2) (a3), Ian B. Hickie (a4), Nicholas G. Martin (a2) and Sarah E. Medland (a2)...

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