A three-stage GWAS was conducted for the patients who underwent painful cosmetic surgery to investigate the association between opioid sensitivity and the 295 036 SNPs that passed the quality control criteria in a total of 353 subjects (118, 117 and 118 subjects for the first-, second- and final-stage analyses, respectively). As an index of opioid sensitivity, postoperative patient-controlled analgesia fentanyl use during the first 24-h postoperative period was used because analgesic requirements likely reflect the efficacy of fentanyl in each individual. To explore the association between the SNPs and phenotype, linear regression analyses were conducted in each stage of the analysis, in which postoperative fentanyl use (μg kg–1; log transformed) and the genotype data of each SNP were incorporated as dependent and independent variables, respectively. Additive, dominant and recessive genetic models were used for the analyses because of the previously 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
