To distinguish the effects of the OPRM1 gene on SI and ND, we made two dichotomous comparisons. For the effect on SI, we compared the genotype and allele frequencies of NS with that of regular smokers including both the Low-ND and High-ND groups. For the effect on ND, we compared the genotype and allele frequencies of the Low-ND group with that of the High-ND group. For individual SNP association analyses, genotype and allele frequencies in the three groups were compared by χ2 test or Fisher's exact test when the expected counts were less than 5 in any cell of the contingency table. Pairwise linkage disequilibrium (LD) was estimated for all subjects by the Haploview 3.2 software [29]. Multi-marker haplotype analyses were conducted with the COCAPHASE module of the UNPHASED program [30].
