We examined association of haplotypes using only the Tagger-defined tagging SNPs (Table 4). For GAD1, the four SNPs form seven haplotypes with frequency greater than 0.01. Three common haplotypes together represent 90% of haplotypes observed. A significant association was found for ISENS with haplotype 2111 (frequency = 0.01) in females, which consisted of a minor allele of marker rs2241165 and common alleles of rs3828275, rs2058725, and rs701492. Again, the negative regression coefficient of this haplotype with ISENS and TOLMX indicated fewer drinks needed to feel subjective effects, in both drinking initiation and heaviest drinking periods, among individuals with this haplotype. In males, the 1121 haplotype (frequency = 0.02) showed association with WDSFS (FDR adjusted P < 0.05) with a negative regression coefficient, indicating a less severe withdrawal syndrome among individuals with this haplotype. However, both associated haplotypes had small frequency (representing 13–25 chromosomes each among our samples), thus the significant haplotypic findings and their true contributions should be taken in caution and larger study is required to confirm these findings. For GAD2, none of the three common haplotypes were significantly associated with alcohol-related traits using criteria of FDR adjusted P < 0.05.
