There are two other clusters of SNPs in GABRR2 (SNPs 44-49 and 54-64) with high LD within each group (r2 > 0.54 and r2 > 0.64 respectively) but little LD between the two groups. There is consistency in the phenotypes associated with the significant SNPs and with the pattern of LD. One SNP from each group was selected for haplotype analysis (rs282121 and rs10944441; r2 = 0.06). The global test of association was significant for the broader COGA phenotype (p = 0.005) and for early onset (p = 0.05) alcohol dependence, and marginally significant for DSM-IV alcohol dependence (p = 0.07) (Table 3b). Haplotype T-G (frequency 38%), consisting of the minor allele of rs282121 and the major allele of rs10944441, was overtransmitted to individuals not meeting any of the three alcohol dependence criteria and its complement, C-A (frequency 12%), was overtransmitted to the individuals meeting COGA (p = 0.002) and DSM-IV (p = 0.044) criteria for alcohol dependence, but not related to early onset.
