Haplotypes were inferred from all six tagging SNPs for both GABRG1 and GABRA2 (Table 4) to evaluate an interactive effect of these genes on risk of AD. The combination of all tagging SNPs yielded 8 haplotypes; each represented ≥2% of observations and together they accounted for 72.2% of the chromosomes among AD subjects and 80.8% among controls. Global analysis showed a nominally significant difference in haplotype frequency between AD and control groups, p=0.00994 (df=7, χ2=18.49). This compares with a Bonferroni-corrected p=0.00625. Specific associations of each common haplotype compared to others were also analyzed. Among these common haplotypes, which spanned 280 kb, the most significant difference was observed in the T-G-C-G-T-A (H8) haplotype (p=0.0033, OR=2.63, 95%CI=1.32-5.54) and accounts for 6.4% of haplotypes in the AD group but only 2.6% in controls. No other haplotype was even nominally significant different between AD subjects vs. controls. Considering the rarity of observations in affecteds and lack of this haplotype in controls, this finding based on estimated haplotype frequencies must be regarded as tentative.
