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

Ebejer, Jane L., Duffy, David L., van der Werf, Julius, Wright, Margaret J., Montgomery, Grant, Gillespie, Nathan A., Hickie, Ian B., Martin, Nicholas G. and Medland, Sarah E. (2013) Genome-wide association study of inattention and hyperactivity-impulsivity measured as quantitative traits. Twin Research and Human Genetics, 16 2: 560-574. doi:10.1017/thg.2013.12


Author Ebejer, Jane L.
Duffy, David L.
van der Werf, Julius
Wright, Margaret J.
Montgomery, Grant
Gillespie, Nathan A.
Hickie, Ian B.
Martin, Nicholas G.
Medland, Sarah E.
Title Genome-wide association study of inattention and hyperactivity-impulsivity measured as quantitative traits
Journal name Twin Research and Human Genetics   Check publisher's open access policy
ISSN 1832-4274
1839-2628
Publication date 2013
Sub-type Article (original research)
DOI 10.1017/thg.2013.12
Open Access Status Not yet assessed
Volume 16
Issue 2
Start page 560
End page 574
Total pages 15
Place of publication Cambridge, United Kingdom
Publisher Cambridge University Press
Language eng
Formatted 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.
Keyword ADHD
Inattention
Hyperactivity-impulsivity
SWAN
GWAS
Meta-analysis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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