Similarly, we performed haplotype-based association analysis for the male sample (Table 4). Altogether, we found that ten haplotypes between SNPs rs16969948 in CHRNA5 and rs11638372 in the intergenic region downstream from the 5′ end of CHRNB4 showed significant associations with at least one smoking-related phenotype. By comparing the haplotype-based association results of the total and male samples, we found six that were comparable in the two samples, except that the association signals appear to be much stronger in the male sample. For example, the P values of associations with SI, SQ, and SC for the haplotype ACT, formed by rs950776-rs11072768-rs7166158 under the dominant model, are, respectively, 0.001, 0.014, and 0.019 in the male sample and 0.013, 0.033, and 0.06 in the total sample. Very interestingly, we found that haplotypes ACT, formed by rs950776-rs11072768-rs7166158, and CTC, formed by rs11072768-rs7166158-rs8043123, were nominally significantly associated with all three smoking-related phenotypes in the male sample, suggesting that this region is a good target for further sequencing analysis with the hope of identifying variants that contribute to our observed association of the cluster with these smoking-related phenotypes.
