In our analysis, there is slightly more evidence for association of OPRM1 SNPs to the nicotine withdrawal sensitivity score in OPRM1 introns, where four SNPs are nominally significantly associated with the nicotine withdrawal sensitivity score in each of the two linkage OPRM1 linkage blocks commonly observed in European ancestry populations (60). Evidence from other studies also suggests that there are potentially two regions of linkage disequilibrium at OPRM1 that may be associated with smoking related phenotypes. In a study investigating associations between 9 OPRM1 SNPs and nicotine dependence in interaction with gender, rs510769 (IVS1+1050) was significantly associated with dichotomized nicotine dependence (P=0.000416) in a sample of 1,929 unrelated ever-smokers with FTND scores of 0, or 4 or more (57). In a study investigating associations between 11 OPRM1 SNPs and nicotine dependence, rs10485057 (IVS3+538) was significantly associated (P=0.0297) with dichotomized nicotine dependence in a sample of 430 unrelated ever-smokers with Fagerström Tolerance Questionnaire (61) scores of 0–2 or 7–11 (20). In addition to studies of OPRM1 variation association with nicotine withdrawal symptoms, dopamine receptor locus sequence variation has been evaluated for
