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Genetic variation in GABRβ1 and the risk for developing alcohol dependence

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. Green open access

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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.

Type: Article
Title: Genetic variation in GABRβ1 and the risk for developing alcohol dependence
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/YPG.0000000000000169
Publisher version: http://doi.org/10.1097/YPG.0000000000000169
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: alcohol dependence, [gamma]-aminobutyric acid receptor, British, GABR[beta]1, genetic association, imputation analysis, Irish, linkage disequilibrium
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst for Women's Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst for Women's Health > Women's Cancer
URI: https://discovery.ucl.ac.uk/id/eprint/1549716
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