Genome-Wide Association Study Identifies Novel Candidate Variants Associated with Postoperative Nausea and Vomiting

SIMPLE SUMMARY: Postoperative nausea and vomiting (PONV) is experienced by approximately 30% of patients who undergo general anesthesia. However, many genetic factors involved in the vulnerability to PONV remain unidentified. The aim of our genome-wide association study (GWAS) was to comprehensively explore genetic variations associated with PONV. We identified several single-nucleotide polymorphisms (SNPs) that may possibly be associated with the frequency of nausea and vomiting, of which the most potent were the rs2776262, rs140703637, rs7212072, rs12444143, rs45574836, and rs1752136 SNPs. These results indicate that these SNPs in the LOC100506403, CNTN5, SHISA6, RBFOX1, ATP8B3, and LOC105370198 gene regions could serve as markers that predict the vulnerability to PONV. ABSTRACT: Considerable individual differences are widely observed in the incidence of postoperative nausea and vomiting (PONV). We conducted a genome-wide association study (GWAS) to identify potential candidate single-nucleotide polymorphisms (SNPs) that contribute to PONV by utilizing whole-genome genotyping arrays with more than 950,000 markers. The subjects were 806 patients who provided written informed consent and underwent elective surgery under general anesthesia with propofol or desflurane. The GWAS showed that two SNPs, rs2776262 and rs140703637, in the LOC100506403 and CNTN5 gene regions, respectively, were significantly associated with the frequency of nausea. In another GWAS conducted only on patients who received propofol, rs7212072 and rs12444143 SNPs in the SHISA6 and RBFOX1 gene regions, respectively, were significantly associated with the frequency of nausea as well as the rs2776262 SNP, and the rs45574836 and rs1752136 SNPs in the ATP8B3 and LOC105370198 gene regions, respectively, were significantly associated with vomiting. Among these SNPs, clinical and SNP data were available for the rs45574836 SNP in independent subjects who underwent laparoscopic gynecological surgery, and the association was replicated in these subjects. These results indicate that these SNPs could serve as markers that predict the vulnerability to PONV. Our findings may provide valuable information for achieving satisfactory prophylactic treatment for PONV.