insufficient knowledge about the genetic factors associated with opioid sensitivity. The GWAS procedure is summarized in Supplementary Figure S1. In the first-stage analysis of 118 subjects, the SNPs that showed statistical P-values of <0.05 were selected as the candidate SNPs for the second-stage analysis among the 295 036 SNPs. For these SNPs, the second-stage analysis was conducted; again, the SNPs that showed P<0.05 were considered potent candidates and selected for further final-stage analysis. In the final stage of the three stages, the Q-values of the false discovery rate were calculated to correct for multiple testing in addition to the P-values based on previous reports.24, 25 The SNPs that showed Q<0.05 in the analysis were considered genome-wide significant.