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 the aforementioned haplotypes contain one or two SNPs of rs16969968, rs1317286, rs6495308, and rs8040868 that were found to have significant associations with ND in previous reports (Berrettini and others 2008; Saccone and others 2007), none of these associations remained significant in the present study after Bonferroni correction. Considering the fact that these subunit genes must assemble together in order to form functional nAChRs, we performed gene–gene interaction analysis on all SNPs in the gene cluster and found the three best interactive models in the AA sample and two in the pooled samples; only those for the AA sample remained significant at the experiment-wide level.