Genomic analysis of surgical patients to identify patients at risk for postoperative sepsis and surgical site infection.

Summary

This large GWAS (n=59,755) identified two loci on chromosomes 9 (rs9413988) and 14 (rs35407594) associated with postoperative sepsis and also linked variants to surgical site infections. The implicated regions lie near PGM5P2/ZNGF1 and the OR11 olfactory receptor family, suggesting regulatory mechanisms. These findings enable genetic risk stratification and hypotheses for mechanistic studies.

Key Findings

• Two loci on chromosomes 9 (rs9413988, p=5.59×10^-12) and 14 (rs35407594, p=1.43×10^-10) reached genome-wide significance for postoperative sepsis.
• Associated SNPs also overlapped with surgical site infection susceptibility.
• Nearby genes (PGM5P2/ZNGF1 and OR11 family) implicate regulatory mechanisms potentially relevant to host response.

Clinical Implications

Preoperative genetic risk stratification could identify patients at high risk for postoperative sepsis/SSI to guide monitoring, prophylaxis, and personalized perioperative management.

Limitations

• No external replication cohort reported
• Phenotype definitions rely on EMR coding, risking misclassification and residual confounding

Future Directions

Replicate findings across ancestries, fine-map causal variants, and integrate functional assays to link variants with immune pathways to inform perioperative risk tools.