McCabe, WA;
Way, MJ;
Ruparelia, K;
Knapp, S;
Ali, MA;
Anstee, QM;
Thomas, HC;
... Morgan, MY; + view all
(2017)
Genetic variation in GABRβ1 and the risk for developing alcohol dependence.
Psychiatric Genetics
, 27
(3)
pp. 110-115.
10.1097/YPG.0000000000000169.
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Knapp_PG-D-16-00067R1 Revised GABRB1 Short Report 4 February2017.pdf - Accepted Version Download (621kB) | Preview |
Abstract
Associations between the [gamma]-aminobutyric acid type-A receptors (GABAA) and alcohol dependence risk have been reported, although the receptor subunit driving the association is unclear. Recent work in mice has highlighted a possible role for variants in the Gabr [beta]1 subunit (Gabr[beta]1) in alcohol dependence risk, although this gene does not contain any common nonsynonymous variants in humans. However, the GABAA receptor is a heteropentamer so multiple potential variants within the gene complex could generate the alcohol dependence phenotype. The association between GABR[beta]1 variants and alcohol dependence risk was explored in a British and Irish population of alcohol-dependent cases (n=450) and ancestrally-matched controls screened to exclude current or historical alcohol misuse (n=555). Twelve common single nucleotide polymorphisms (SNPs) and a rare nonsynonymous variant, rs41311286, were directly genotyped; imputation was then performed across the whole gene. No allelic association was observed between alcohol dependence risk and any of the directly genotyped or imputed SNPs. However, post-hoc testing for genotypic association identified five common intronic SNPs that showed modest evidence for association after correction for multiple testing; two, rs76112682 and rs141719901, were in complete linkage disequilibrium [Pcorrected=0.02, odds ratio (95% confidence interval)=5.9 (1.7-2.06)]. These findings provide limited support for an association between GABR[beta]1 and the risk for developing alcohol dependence; further testing in expanded cohorts may be warranted.
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