Interpopulation linkage disequilibrium patterns of GABRA2 and GABRG1 genes at the GABA cluster locus on human chromosome 4

GABRA2 and GABRG1, which encode the alpha-2 and gamma-1 subunits, respectively, of the GABA(A) receptor, are located in a cluster on chromosome 4p. The GABRA2 locus has been found to be associated with alcohol dependence in several studies, but no functional variant that can account for this association has been identified. To understand the reported associations, we sought to understand the linkage disequilibrium (LD) patterns and haplotype structures of these genes. With close intergenic distance, approximately 90 kb, it was anticipated that some markers might show intergenic LD. Variation in 13-SNP haplotype block structure was observed in five different populations: European American, African American, Chinese (Han and Thai), Thai, and Hmong. In the Hmong, a 280-kb region of considerably higher LD spans the intergenic region, whereas in other populations, there were two or more LD blocks that cross this region. These findings may aid in understanding the genetic association of this locus with alcohol dependence in several populations.