In the analysis of the patients who underwent major abdominal surgery, the calculated total dose of rescue analgesics administered during the first 24-h postoperative period was used as an index of opioid sensitivity. To explore the association between the SNPs and phenotype, Student's t-test or analysis of variance was performed, in which Bonferroni correction for multiple comparisons was used for the post hoc tests. For these analyses, postoperative analgesic use (μg kg–1; log transformed) and the genotype data of each SNP were incorporated as dependent and independent variables, respectively. χ2 Tests were performed to investigate the contribution of the SNPs to the vulnerability to the presence of serious symptoms of substance dependence. For the analyses in which the number of subjects in a cell in 2 × 2 contingency tables was <5, Fisher's exact tests were conducted instead of χ2 tests. In the analysis of healthy volunteers with personality profile data, raw TCI scores were properly processed (see Supplementary Information). To explore the association between the SNPs and phenotype, linear regression analyses were conducted, in which the endpoint TCI score
