Inter-population linkage disequilibrium (LD) patterns of GABRA2 and GABRG1 genes at the GABA cluster locus on human chromosome 4

摘要

GABRA2and GABRG1, which encode the α2 and γ1 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 (AD) in several studies, but no functional variant that can account for this association has been identified. In order to understand the reported associations, we sought to understand LD patterns and haplotype structure of these genes. With close intergenic distance, ~90 kb, it was anticipated some markers might show intergenic LD. Variation in 13-SNP haplotype block structure was observed in 5 different populations: European American, African American, Chinese [Han and Thai], Thai, and Hmong. In Hmong, a 280 kb region of considerably higher LD spans the intergenic region, whereas in other populations, there were two or more LD blocks cross this region. These findings may aid in understanding genetic association of this locus with alcohol dependence in several populations.