To examine the effect of CNR1 genotypes on SI and ND, we compared the allele frequencies of typed SNPs between nonsmokers and smokers and between low- and high-ND smokers, respectively. Of the 10 SNPs, rs6928499 and rs2023239 showed nominally significant associations for both SI and ND (Table 2). For both markers, the major alleles, G and T, respectively, were overrepresented in cases. To evaluate whether sex plays a role in the association, we used a computer program (UNPHASED) and used sex as a modifier covariate. In these analyses, rs6928499 showed nominally significant results for both main effect and sex effect for SI (Table 3) but only a significant main effect for ND; rs2023239 showed similar association but with weaker signal strength. Another 2 SNPs, rs1049353 and rs12720071, showed similar female-specific associations with ND.
