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Genetic variation in GABRβ1 and the risk for developing alcohol dependence

Lookup NU author(s): Professor Quentin AnsteeORCiD

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Abstract

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. 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 β1 subunit (Gabrβ1) 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 GABRβ1 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 GABRβ1 and the risk for developing alcohol dependence; further testing in expanded cohorts may be warranted. Psychiatr Genet 27:110-115

Publication metadata

Author(s): McCabe WA, Way MJ, Ruparelia K, Knapp S, Ali MA, Anstee QM, Thomas HC, McQuillin A, Morgan MY

Publication type: Article

Publication status: Published

Journal: Psychiatric Genetics

Year: 2017

Volume: 27

Issue: 3

Pages: 110-115

Online publication date: 01/06/2017

Acceptance date: 20/02/2017

ISSN (print): 0955-8829

ISSN (electronic): 1473-5873

Publisher: Lippincott Williams and Wilkins

URL: https://doi.org/10.1097/YPG.0000000000000169

DOI: 10.1097/YPG.0000000000000169

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