Chunk #18 — Results — Identification of a potent locus associated with human opioid sensitivity by GWAS in subjects who underwent painful cosmetic surgery
We first explored the association between genetic variations and opioid sensitivity in a total of 353 healthy subjects who were scheduled to undergo cosmetic orthognathic surgery (mandibular sagittal split ramus osteotomy) for mandibular prognathism that involved the administration of opioid analgesics (Supplementary Table S1), in which the surgical procedure was uniform and thus the invasiveness and resultant pain would be regarded as homogeneous among the subjects. A GWAS was conducted as a consecutive three-stage analysis to identify potent SNPs associated with the requirements for an opioid analgesic, fentanyl (μg kg–1), during the 24-h postoperative period (Supplementary Figure S1). Consequently, 9, 12 and 10 SNPs were selected as the top candidates for additive, dominant and recessive models for each minor allele, respectively, after the final stage (Supplementary Tables S2–4). Among these, several SNPs mapped to 2q33.3–2q34 showed significant associations after the final stage with 24-h postoperative fentanyl requirements in the additive and recessive models (additive model: combined β=0.293, nominal P=8.044 × 10−7; recessive model: combined β=0.553, nominal P=9.382 × 10−7; Supplementary Tables S2–4). The observed P-values of these SNPs, calculated as
