Using the FBAT program, we performed haplotype-based association analysis for all possible haplotypes in consecutive three-SNP combinations for the three ND measures. In the combined sample, we found a major haplotype, T-A-C, formed by SNPs rs17408276, rs16969968, and rs615470 in CHRNA5 at a frequency of 14%, that was significantly associated with SQ (P = 0.018) and HSI (P = 0.019) under the additive model (Table 3). We also found three major haplotypes in CHRNA3, G-C-T (11%; formed by rs1317286, rs12914385, and rs2869546), C-G-C (34%; formed by rs6495308, rs3743075, and rs8040868), and A-T-T (36%; formed by rs3743075, rs8040868, and rs6495309), which showed significant association with at least two of the three ND measures (P = 0.016 ~ 0.047; Table 3). However, none of these associations remained significant after correction for multiple testing of major haplotypes.
