We also assessed the association of previously reported loci using our GWAS data (Table S6). Interestingly, while previous studies indicated that the region with the strongest association with CPD was the 15q25 cluster, which encompasses the CHRNA3, CHRNA5 and CHRNB4 genes [4]–[6], our study revealed that the CYP2A6 locus has the strongest association with CPD in the Japanese population. The 15q25 cluster includes genes coding for nicotinic acetylcholine receptors; however, the Japanese population seems to have less genetic variation in this area than the European population ( i.e., a lower minor allele frequency at the CPD associated locus; Table S6). It is also interesting that the common deletion at the CYP2A6 locus was significant in the Japanese population but not in the European population [14]. These findings suggest that there might have been a strong selective pressure [23] on the 15q25 locus in the Japanese population and on the CYP2A6 locus in the European population, although no evidence for this selection has been observed using the HGDP selection browser (see URLs).
