While alcoholism GWAS studies await further validation, some of the candidates coming out of these earlier human genetic approaches have support from work in animal model systems, and therefore seem like potentially stronger alcoholism risk candidate genes. Animal models support the human genetic studies implicating the γ-aminobutyric acid (GABA) system as fundamentally involved in alcohol intoxication, withdrawal, and other behavioral aspects of alcoholism (Krystal et al., 2006). Ethanol enhances GABAA receptor function (Bowen et al., 1998) and electrophysiologic studies implicate GABAA receptors as targets for the effect of ethanol in the central nervous system (Suzdak et al, 1986). Multiple candidate gene reports show an association between variants in GABRA2 and alcohol dependence (Enoch, 2008). In a hypothesis driven approach to test this association as part of a GWAS study, we find a modest association with GABRA2 (OR=1.1 and p value ~0.01), further supporting the role of this candidate gene in the development of alcoholism.
