In the current study, we examined the genetic associations and interactions between variations in the CHRNA5/A3/B4 gene cluster and ND in two independent samples. Individual SNP-based association analyses revealed that rs8040868 in CHRNA3 was significantly associated with all the ND measures in the AA sample and with SQ in the combined sample, whereas rs1317286 revealed relationships with SQ and HSI in the combined sample. We also performed haplotype-based association analyses on all SNPs using a sliding window approach. In the CHRNA3 gene, one common haplotype (G-C-T) for SNPs rs1317286-rs12914385-rs2869546 in the combined and AA samples showed a significant positive association with ND. Moreover, we found haplotypes C-G-C/T, formed by rs6495308, rs3743075, and rs8040868, and A/G-T-T, formed by rs3743075, rs8040868, and rs6495309 in CHRNA5, to have a marginal association with ND in the combined and EA samples. Haplotype T-A-C, formed by rs17408276-rs16969968-rs615470 in CHRNA5, was significantly associated with SQ and HSI in the combined sample and only HSI in the EA sample, whereas the allelic T-G-C of this haplotype showed an inverse association with HSI in the EA sample. Although all
