Linkage analysis of multiplex families recruited in the Collaborative Study on the Genetics of Alcoholism identified a region on chromosome 4p that was linkage to alcohol dependence41; linkage in this region was supported by other studies42. SNP genotyping was performed in candidate genes within the linked region – notably in the GABAA receptor genes. A group of SNPs within the GABRA2 (γ-amino butyric acid receptor A2) gene, which were in high linkage disequilibrium with each other (i.e. tightly correlated), were associated with alcohol dependence and appeared at least in part to underlie the observed linkage finding43. This association has been replicated in many different samples of European44-47 and African ancestry48. The finding was strongest in alcoholics with early onset or comorbid drug dependence45, 49. There is evidence that the association may extend beyond GABRA2 and may also include the adjacent GABRG1 gene50, 51. Analyses raise the possibility that there may be distinct effects in each gene48, 50 or there may be long range haplotypes that contribute to the risk of alcohol dependence52.
