The most robust candidate gene finding to date is for GABRA2 that was initially identified by linkage scans [41–43]. The GABAA gene cluster on chromosome 4 includes GABRA2, GABRG1 and GABRB1 that together encode the α1β1γ1 receptor that is almost exclusively found in the reward pathway. The initial finding came from COGA. This study showed a strong association between GABRA2 SNPs and alcoholism and resting EEG beta power [46]. Since then numerous studies, nearly all in Caucasians, have replicated this association although there have also been negative findings [47]. These studies have all identified the same two GABRA2 haplotype blocks, at least within Caucasians, American Indians and Asians. The significant association signals have been with the two, similar frequency yin yang haplotypes within the distal haplotype block. Many of the SNPs in allelic identity are conserved across species indicating the likelihood of selective pressure for this GABRA2 region distal to intron 3 [47]. Two subsequent studies in the COGA dataset have shown that the original evidence for association with AUD derived only from individuals with comorbid illicit drug dependence [48]
