As yet, no functional GABRA2 locus has been identified. Moreover, a recent study has shown significant haplotype and SNP association with alcoholism in a haplotype block that extends from the intergenic region between GABRA2 and GABRG1 up to GABRG1 intron 3 in two large groups of U.S. Caucasians but not in African Americans (Covault et al, 2008). Thus it is possible that the apparent GABRA2 association with alcoholism may be due to linkage disequilibrium (LD) with a functional variant in GABRG1. The aim of our study was therefore firstly to examine the association between GABRG1 and alcoholism in Finnish Caucasians and Plains American Indians, two population isolates in which we had previously found a GABRA2 association with alcoholism that was mediated by anxiety (Enoch et al, 2006a). Secondly, since HapMap (http://www.hapmap.org/) has identified long-distance LD across the two adjacent genes, we investigated whether there were long-distance haplotypes spanning GABRA2 and GABRG1 that were common to both population isolates, i.e. ancestral haplotypes. To this end we genotyped 24 SNPs spanning GABRG1 from one intergenic region to the other and included two previously genotyped tag SNPs for the GABRA2 risk haplotypes.
