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Title: Genome-Wide Association Study of Inattention and Hyperactivity-Impulsivity Measured as Quantitative Traits
Contributor(s): Ebejer, Jane (author); Duffy, David L (author); Van Der Werf, Julius H  (author)orcid ; Wright, Margaret J (author); Montgomery, Grant W (author); Gillespie, Nathan A (author); Hickie, Ian B (author); Martin, Nicholas (author); Medland, Sarah (author)
Publication Date: 2013
Open Access: Yes
DOI: 10.1017/thg.2013.12Open Access Link
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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 × 10ˉ⁷) for symptoms of hyperactivity-impulsivity. The strongest effect in the gene-based test was for GPR139 on symptoms of inattention (6.40 × 10ˉ⁵). Replication of this study with larger samples will add to our understanding of the genetic etiology of ADHD.
Publication Type: Journal Article
Source of Publication: Twin Research and Human Genetics, 16(2), p. 560-574
Publisher: Cambridge University Press
Place of Publication: United Kingdom
ISSN: 1839-2628
Field of Research (FOR): 060412 Quantitative Genetics (incl Disease and Trait Mapping Genetics)
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
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