Regular smokers with high ND (High-ND) were those who smoked for five years or more and had an FTQ score between 7–11. In order to evaluate separately the influence of OPRM1 on SI and ND, two measurements with overlapping but not identical genetic effects [21,23], we used this 3-group design. The selection of subjects was based on this design. To estimate the influence of OPRM1 on SI, we compared the allele and genotype frequencies between the NS and regular smokers (which included both Low- and High-ND subjects). For that of ND, we compared the frequencies between the Low- and High-ND subjects. Smokers with FTQ scores between 2 and 7 were not used in this dichotomized design. Of the 688 subjects used in this study, 244 were NS, 215 were Low-ND and 229 were High-ND.