One SNP from each of these latter two groups was selected (rs914479 and rs282129; r2 = 0.42) and used in haplotype analysis to test whether a high risk haplotype could be identified within the region spanned by SNPs 27-37. The global test of significance was significant for all three alcohol dependence phenotypes: DSM-IV (p = 0.016), COGA (p = 0.014), and early onset (p = 0.030) (Table 3a). For all three phenotypes, a common haplotype having a frequency of 61% (T-G) was associated with the absence of alcohol dependence (p < 0.008 for DSM-IV; p < 0.007 for COGA; p = 0.019 for early onset. The complementary haplotype C-A, consisting of the minor alleles of both SNPs, was associated with COGA alcohol dependence (p = 0.02) and showed a trend toward significant association with DSM-IV (p = 0.11); the low frequency of this haplotype gives it lower power.
