What this means

GABRA2 codes for the α2 subunit of the GABA-A receptor — the brain's main brake. Alcohol acts as a positive modulator of GABA-A receptors, which is part of why drinking is sedating and anxiolytic. Variants in GABRA2 (rs279858 is the most-cited tag SNP) were originally identified by COGA (Edenberg et al., 2004) as associated with alcohol dependence, and have been replicated in multiple subsequent cohorts. The effect size is small — odds ratios in the 1.1–1.3 range — but the signal is one of the more durable common-variant findings in the addiction genetics literature. GABRA2 has also been linked to childhood externalising behaviour and to anxiety phenotypes, suggesting the receptor's role spans more than just alcohol.

GABRA2 makes part of the brain's main "calm down" receptor. Alcohol pushes that receptor harder, which is a big part of why a drink feels relaxing. A common DNA change in this gene was first linked to problems with alcohol in a large family study (COGA), and the finding has been replicated since. The effect on any one person is small — most people with the risk version never develop a problem with alcohol, and many people without it do. But the result is one of the more reliable common-variant findings in alcohol genetics, and the same receptor is also tied to childhood self-control and anxiety, so the biology is broader than just drinking.

Caveats

• Effect size on individual risk is small (odds ratios ~1.1–1.3).
• The risk language is about *average* risk; this is not predictive at the individual level.
• GABRA2 variants are also linked to anxiety and externalising behaviour — alcohol is one phenotype among several.
• Most studied in European-ancestry cohorts.

Populations

• First reported in the COGA (Collaborative Study on the Genetics of Alcoholism) European-ancestry sample; replicated across several populations

References

• Edenberg et al. — Variations in GABRA2, encoding the α2 subunit of the GABAA receptor, are associated with alcohol dependence and with brain oscillations (American Journal of Human Genetics, 2004)
• Covault et al. — Allelic and haplotypic association of GABRA2 with alcohol dependence (American Journal of Medical Genetics, 2004)
• Enoch — The role of GABA(A) receptors in the development of alcoholism (Pharmacology Biochemistry and Behavior, 2008)