Linkage disequilibrium haplotype and association studies of a chromosome 4 GABA receptor gene cluster: candidate gene variants for addictions

摘要

Strong genetic contributions to individual differences in vulnerability to addictions are well supported by classical genetic studies. Linkage and association genome scans for addiction vulnerability have provided converging evidence for several chromosomal regions which are likely to harbor allelic variants that contribute to such vulnerability. We and others have delineated a candidate addiction-associated chromosome 4p12 “rSA3” region based on convergent data from association genome scanning studies in polysubstance abusers (), linkage based studies in alcoholism (; ) and association-based studies for alcoholism and association-based studies for individual differences in electroencephalographic (EEG) spectral power phenotypes (; ). The rSA3 region contains interesting candidate genes that encode the alpha 2, alpha 4, beta 1 and gamma 1 receptor subunits for the principal brain inhibitory neurotransmitter, GABA (; ; ). We now report assessment of single nucleotide polymorphism (SNP) genotypes in this region in three samples of substance abusers and controls. These results delineate the haplotypes and patterns of linkage disequilibrium in this region, focus attention of the GABRA2 gene and identify modest associations between GABRA2 genotypes and addiction phenotypes. These results are consistent with modest roles for GABRA2 variants in addiction vulnerabilities.