DESCRIPTION:

The results of individual GWAS for inattention, hyperactivity–impulsivity, and combined symptoms within each study were combined in a meta-analysis using Meta-Analysis Helper (Metal; Abecasis & Willer, 2007). Gene-based test results of SNP effects from meta-analysis of MN and NU combined, inattentive, and hyperactive-impulsive symptoms. The results of the meta-analysis were examined for gene-based association using Versatile Gene-based Association Study (VEGAS; Liu et al., 2010) to estimate the combined effect of all markers within ±50 kb of 5’ and 3’ untranslated regions of a gene. The significance level required for the gene-based test is p<2.8E-6 (.05/17,787 autosomal genes).

LABEL:

Gene-based ADHD association GWAS inattention symptom_pvalue

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.5

GENES IN THRESHOLD:

7

DATE ADDED:

2025-01-14

DATE UPDATED:

2025-01-14

SPECIES:

AUTHORS:

Ebejer JL, Duffy DL, van der Werf J, Wright MJ, Montgomery G, Gillespie NA, Hickie IB, Martin NG, Medland SE

TITLE:

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

JOURNAL:

Twin research and human genetics : the official journal of the International Society for Twin Studies Apr 2013, Vol 16, pp. 560-74

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. PUBMED: 23527680
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