phenotypes, are related to the pain-sensitivity haplotype established by our analysis. SNP rs1799971 (A118G) has been repeatedly shown to produce functional effects. Carriers of the minor 118G allele show decreased analgesic responses to morphine and M6G (22–25) and significantly higher pressure pain thresholds (26). In our dataset, homozygotes for the G allele tended to have the lower mean pain scores, whereas homozygotes for the A allele tended to have the higher mean pain scores (data not shown), but this difference did not achieve significance. We also considered rs495491, which has been associated with pain-related mood scores (58), and rs609148, which along with rs495491 has been shown to be associated with substance dependence, including opioid dependence (57). We evaluated the 6-loci haplotypes consisting of the three core SNPs established by our analysis and three SNPs described in the literature: rs1799971 (A/G), rs495491 (A/G), rs563649 (C/T), rs2075572 (G/C), rs533586 (C/T) and rs609148 (G/A). The D′ values between rs563649 and this set of SNPs are also very high (1, 1, 0.81, 1, 1, 1) (Supplementary Material, Fig. S3). The 6-loci haplotype A-G-T-C-T-G was also found to be significantly associated with higher pain scores (z = 4.83) and was also observed in 6% of
