Extensive LD across the CHRNA5-CHRNA3-CHRNB4 cluster led to multiple significant SNPs in our data. After accounting for the LD structure in this region, we identified two distinct, significant associations tagged by rs16969968 and rs578776. Therefore, genotypes at these SNPs were entered together into a multivariate logistic regression model to evaluate the significance of the effect of one locus when controlling for genotype at the other locus. Additionally, the combined influence of the two-locus genotype was examined in a 3×3 table.