To distinguish the effects of the CNR1 gene on SI and ND, we made 2 dichotomous comparisons. For the effect on SI, we compared the allele frequencies of nonsmokers with that of regular smokers in both the low- and high-ND groups. For the effect on ND, we compared the allele frequencies of the low-ND group with that of the high-ND group. For individual SNP association analyses, allele frequencies in the 3 groups were compared by the χ2 test or Fisher exact test when the expected counts were less than 5 in any cell of the contingency table. Sex-stratified analyses and multimarker haplotype analyses were conducted with the UNPHASED program (version 3.06),52 which uses a log-likelihood retrospective regression model. In the sex-stratified analyses, sex was used as a modifier covariate, and either the male or female was used as baseline. In these analyses, both main effect and sex effect were estimated in a single test. The SNP spectral decomposition (SNPSpD) method53 was used to evaluate the equivalent number of independent tests, and Bonferroni correction was applied for multiple testing correction. Pairwise
