Genome-wide association study on chronic postsurgical pain in the UK Biobank.
Summary
In a UK Biobank GWAS of 95,931 surgical patients, a locus within GLRA3 reached genome-wide significance for chronic postsurgical pain. GLRA3 is implicated in prostaglandin E2 pain pathways, and the authors release summary statistics, while emphasizing the need for external validation.
Key Findings
- GLRA3 showed genome-wide significant association with chronic postsurgical pain in case-control analysis.
- GLRA3 is involved in prostaglandin E2-induced pain processing pathways, supporting biological plausibility.
- Summary statistics are provided to facilitate replication and mechanistic studies; external validation is needed.
Clinical Implications
Immediate practice change is not warranted, but risk stratification tools and PGE2/GLRA3-related pathways may inform future preventive analgesia strategies and trial design.
Why It Matters
This is one of the largest genetic studies of CPSP, revealing a biologically plausible locus and enabling precision pain research. It provides a mechanistic anchor for future target discovery.
Limitations
- Phenotype definitions rely on postoperative analgesic use and may introduce misclassification.
- Heterogeneity across surgical procedures and lack of independent replication within the study.
Future Directions
Replicate associations in independent, phenotypically rich cohorts; perform fine-mapping, functional assays, and clinical translation for risk prediction and targeted analgesia.
Study Information
- Study Type
- Case-control
- Research Domain
- Pathophysiology
- Evidence Level
- III - Large genetic association study using a case-control GWAS design
- Study Design
- OTHER