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Genetic variation in GABRβ1 and the risk for developing alcohol dependence.
William A McCabe1, Michael J Way, Kush Ruparelia
1aUCL Institute for Liver & Digestive Health, Division of Medicine bMolecular Psychiatry Laboratory, Division of Psychiatry, University College London cDepartment of Gastroenterology and Hepatology, Imperial College, St Mary's Hospital Campus, London dInstitute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Psychiatric Genetics
|March 28, 2017
Summary
This study investigated the GABRβ1 gene
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Alcohol dependence has known associations with gamma-aminobutyric acid type-A receptors (GABAA).
- The specific GABAA receptor subunit contributing to alcohol dependence risk remains unclear.
- Mouse studies suggest a potential role for the Gabr β1 subunit (Gabrβ1) in alcohol dependence risk.
Purpose of the Study:
- To explore the association between GABRβ1 variants and alcohol dependence risk in a British and Irish population.
- To investigate both common and rare variants within the GABRβ1 gene.
- To determine if GABRβ1 genetic variations contribute to the risk of developing alcohol dependence.
Main Methods:
- Genotyping of 12 common single nucleotide polymorphisms (SNPs) and one rare nonsynonymous variant (rs41311286) in GABRβ1.
- Imputation analysis across the entire GABRβ1 gene.
- Case-control study involving 450 alcohol-dependent individuals and 555 controls.
Main Results:
- No allelic association was found between GABRβ1 variants and alcohol dependence risk.
- Post-hoc genotypic analysis revealed modest evidence of association for five common intronic SNPs.
- Two SNPs (rs76112682 and rs141719901) showed significant association after multiple testing correction (Pcorrected=0.02, OR=5.9).
Conclusions:
- Findings provide limited support for an association between GABRβ1 and alcohol dependence risk.
- The identified intronic SNPs may warrant further investigation.
- Larger cohort studies are recommended to confirm these preliminary findings.
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