Genome-wide association study on chronic postsurgical pain in the UK Biobank

Background: Chronic postsurgical pain (CPSP) persists beyond the expected healing period after surgery, imposing a substantial burden on overall patient well-being. Unfortunately, CPSP often remains underdiagnosed and undertreated. To better understand the mechanism of CPSP development, we aimed to identify genetic variants associated with CPSP. Methods: A genome-wide association study was conducted in a cohort of 95,931 individuals from the UK Biobank who had undergone different surgical procedures. Three analyses were performed: (1) case-control analysis (2923 cases with CPSP and 93,008 controls), (2) ordinal analysis in three groups based on time of analgesics use (n=95,931), and (3) a meta-analysis combining our dataset with a recent publication (n=97,281). Results: In the case-control analysis, one genetic locus within GLRA3 displayed a genome-wide significant (P<2.5x10(-8)) association with CPSP, and nine loci displayed suggestively significant associations (P<1x10(-6)). The ordinal analysis aligned with the case-control analysis, with an additional locus (rs140330443) reaching genome-wide significance. In the meta-analysis with the recently published dataset, the single nucleotide polymorphism (SNP) rs17298280 in the GLRA3 gene remained significant (P=2.19x10(-9)). Conclusions: This study contributes new insights into the genetic factors associated with CPSP. The top hit GLRA3 is known for involvement in prostaglandin E2-induced pain processing pathways. Our study provides a foundation for future investigations into the function of these risk variants and the mechanisms underlying CPSP by offering summary statistics. However, further validation in other cohorts is required to confirm these findings.