The pattern of LD across these genes suggests that there are at least 6 different regions of association (Figure 3), and that there may be several different susceptibility haplotypes in this region. Between the 5′ region of GABRR1 and the 3′ end of GABRR2, we detected a haplotype (rs914479[T] - rs282129[G]) that appears to confer protection against all three phenotypes of alcohol dependence (Table 3). This region includes the coding SNP rs282129. A haplotype within the coding and proximal 5′ portion of GABRR2 (rs282121[T] - rs1094441[G]) also appears to confer protection from alcohol dependence (Table 3). We detected strong evidence of association of the complementary haplotype rs282121[C] - rs1094441[A] to COGA criteria for alcohol dependence (p = 0.002), less evidence of association with the narrower DSM-IV criteria (p = 0.044) but no evidence of association with the early onset subset of our sample; this pattern suggests that the C-A haplotype confers risk for alcoholism but not particularly for the more severe manifestations.
