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

Kaleem S Ahmed; Mathias A Christensen; Alexander Bonde; Wei-Qi Wei; Atlas Khan; Jennifer Pacheco; Megan Roy-Puckelwartz; Robert J McCarthy; Hasan B Alam; Martin Sillesen

doi:10.1097/TA.0000000000004530

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

J Trauma Acute Care Surg. 2025 Jan 6. doi: 10.1097/TA.0000000000004530. Online ahead of print.

Authors

Kaleem S Ahmed¹, Mathias A Christensen, Alexander Bonde, Wei-Qi Wei, Atlas Khan, Jennifer Pacheco, Megan Roy-Puckelwartz, Robert J McCarthy, Hasan B Alam, Martin Sillesen

Affiliation

¹ From the Division of Trauma and Critical Care, Department of Surgery (K.S.A.), Feinberg School of Medicine, Northwestern University, Illinois; Department of Surgery (K.S.A.), School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin; Department of Organ Surgery and Transplantation (M.A.C.) and Department of Organ Surgery and Transplantation (A.B.), University of Copenhagen, Copenhagen, Denmark; Department of Surgery (W.-Q.W.), Vanderbilt University Medical Center, Tennessee, Nashville; Department of Surgery (A.K.), Columbia University Medical Center, New York; Center for Genetic Medicine (J.P., M.R.-P.), Feinberg School of Medicine, Northwestern University; Department of Anesthesiology (R.J.M.), Rush University Medical Center; Division of Trauma and Critical Care, Department of Surgery (H.B.A.), Feinberg School of Medicine, Northwestern University, Chicago, IL; and Department of Organ Surgery and Transplantation (M.H.S.), University of Copenhagen, Copenhagen, Denmark.

PMID: 39760666
DOI: 10.1097/TA.0000000000004530

Abstract

Background: Early and accurate diagnosis of sepsis and the ensuing organ dysfunction remain a challenge in the postoperative setting. Susceptibility to infections, as well as the subsequent immunological response, are driven to some extent by the genetic predisposition of the patient. The purpose of this study was to identify novel genetic variants associated with postoperative sepsis (POS) and surgical site infections (SSIs).

Methods: We conducted genome-wide association studies for POS and SSIs in the Electronic Medical Records and Genomics Network database. All patients with surgical and genomic information in Electronic Medical Records and Genomics were identified. Patients with a new diagnosis of sepsis/SSIs after surgery were classified as cases, and those without as controls. Analyses were performed using PLINK 2.0's logistic regression function. A p value of <5 × 10-8 was considered statistically significant.

Results: A total of 59,755 participants were included in the analysis. Genetic regions on chromosomes 9 and 14 reached statistical significance for POS (p < 5 × 10-8). The most significant single-nucleotide polymorphisms (SNPs) were rs9413988 (p = 5.59 × 10-12) on chromosome 9 and rs35407594 (p = 1.43 × 10-10) on chromosome 14. The rs9413988 region is downstream to the phosphoglucomutase 5 pseudogene (PGM5P2) and Zn-regulated GTPase metalloprotein activator 1F (ZNGF1) and likely plays a role in transcription regulation, while rs35407594 corresponds to the olfactory receptor gene family, OR11. Similar SNPs were also associated with SSIs.

Conclusion: We have identified two genetic regions containing SNPs associated with POS and SSIs. These findings provide new avenues for investigation, which may help identify and guide point-of-care management for at-risk patients.

Level of evidence: Prognostic and Epidemiological; Level III.