In sum, this is the first genetic study aimed at investigating any association of the variants of the CHRNA5/A3/B4 cluster with SI, SQ, and SC in Korean smokers. Despite the caveats regarding correction for multiple testing, our replication of prior reported significant associations of CHRNA5/A3/B4, combined with the convergent biological data implicating the functional roles of nAChR subunit genes residing in this cluster in addiction, strengthens the notion that the multiple nominally significant association signals we detected at both the SNP and haplotype levels in the Korean sample are true positives. Moreover, our study is the first to show that the nominally significant association signals have extended beyond the 5′ end of CHRNB4 to the flanking intergenic region. Further, we found that the associations of this cluster region with SI and SQ phenotypes appeared to be stronger than those with the SC phenotype in Koreans smokers. Finally, we provided evidence for nominally significant interactions among variants studied in affecting SI in the male sample. Although these findings are novel and encouraging, they do need to be confirmed in larger, independent studies of subjects with Asian ancestry.
