This is the first study reporting evidence of association between GABRR1 and GABRR2 and alcohol dependence. Our primary analysis, using DSM-IV criteria as the phenotype, gave evidence of association primarily in GABRR2 (5 significant and 6 suggestive SNPs; Figure 1, Table 2). Among the associated SNPs, rs282129 is a non-synonymous coding SNP in exon 9 of GABRR2; the major allele (C) encodes Thr430 in transmembrane domain 4, which forms part of the ion channel, and the minor allele (T) encodes Met430. Met is overtransmitted to alcoholic individuals, suggesting that the protein with Met430 might differ in function in a way that might contribute to the development of alcohol dependence. However, this cSNP is in a larger region of LD extending to the upstream region of GABRR1, thus it could be that other regulatory variations in the region are responsible for the association..
