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

Ebejer, Jane; Duffy, David L; Van Der Werf, Julius H; Wright, Margaret J; Montgomery, Grant W; Gillespie, Nathan A; Hickie, Ian B; Martin, Nicholas; Medland, Sarah

doi:10.1017/thg.2013.12

Author(s)

Ebejer, Jane

Duffy, David L

Van Der Werf, Julius H

Wright, Margaret J

Montgomery, Grant W

Gillespie, Nathan A

Hickie, Ian B

Martin, Nicholas

Medland, Sarah

Publication Date

2013

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.

Citation

Twin Research and Human Genetics, 16(2), p. 560-574

ISSN

1839-2628

1832-4274

Link

https://hdl.handle.net/1959.11/14498

Language

en

Publisher

Cambridge University Press

Title

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

Type of document

Journal Article

Entity Type

Publication

Author(s)	Ebejer, Jane Duffy, David L Van Der Werf, Julius H Wright, Margaret J Montgomery, Grant W Gillespie, Nathan A Hickie, Ian B Martin, Nicholas Medland, Sarah
Publication Date	2013
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.
Citation	Twin Research and Human Genetics, 16(2), p. 560-574
ISSN	1839-2628 1832-4274
Link	https://hdl.handle.net/1959.11/14498
Language	en
Publisher	Cambridge University Press
Title	Genome-Wide Association Study of Inattention and Hyperactivity-Impulsivity Measured as Quantitative Traits
Type of document	Journal Article
Entity Type	Publication

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

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