In the current study, we examined genetic associations and epistatic variants in CHRNA5/A3/B4 with SI, SQ, and SC in the total and male samples. Individual SNP-based association analyses revealed that seven SNPs within this region showed significant associations with at least one smoking behavior in either or both samples. Of these polymorphisms, rs951266 in CHRNA5 showed the strongest association with SI (P = 0.006) and SQ (P = 0.001) and rs11072768 in CHRNB4 with all the three smoking-related phenotypes in the total (SI: P = 0.015; SQ: P = 0.028; SC: P = 0.018) and male (SI: P = 0.001; SQ: P = 0.016; SC: P = 0.010) samples. Furthermore, we found multiple haplotypes between rs16969948 in CHRNA5 and rs6495316 or rs11638372 in the intergenic region downstream from the 5′ end of CHRNB4 that were associated significantly with the three smoking-related phenotypes in both the total and the male sample. Finally, considering the fact that the protein products of these nAChR subunit genes must assemble in order to form functional nAChRs, we also performed gene-gene interaction analysis on all SNPs
