Several SNPs in a gene called GABRA2, which encodes the α2-subunit of the GABA receptor, have been associated with alcohol dependence. The first study to implicate GABRA2 in the etiology of alcoholism was conducted by Edenberg and colleagues (2004), who found an association between multiple SNPs (in moderate to high correlation with each other) and alcohol dependence. These results initially were replicated by multiple independent efforts (Drgon et al. 2006; Fehr et al. 2003; Lappalainen et al. 2005; Soyka et al. 2008); however, other investigators could not replicate the findings (e.g., Lind et al. 2008). In contrast to the variants in the alcohol-metabolizing genes, the GABRA2 variants that are associated with alcohol dependence do not change the amino acid sequence in the encoded protein but instead likely alter the regulation of GABRA2 protein production.
