Analysis of current CPD, which was much less powered than lifetime CPD due to a lower number of subjects, was still able to detect some evidence of association with markers near CYP2A6, yet not for those located in the CHRNA3/CHRNA5 region. CYP2A6 is an enzyme primarily responsible for conversion of nicotine to cotinine in the liver, and rs1801272 (Leu160His) codes for the CYP2A6*2 allele, which inactivates the enzyme.41 This SNP showed the largest effect size on both current and lifetime average CPD among all analyzed candidate SNPs in the region. Leu160His is in LD (D’=1.0) with other SNPs that were replicated in the CYP2A6 locus. This agrees with previous GWAS and suggests that the rs1801272 SNP may be a true causative variant, while the other associations observed may be due to partial tagging by this SNP.8 Importantly, we show that the genotyped proxy SNPs in the CYP2A6 locus confirmed our analysis on imputed SNPs with respect to lifetime average CPD. The lack of convincing association for the proxy SNP rs7251418 with current CPD may be explained by the relatively smaller
