Novel polygenic risk score associates with diverticulitis in a multi-institutional, ancestrally diverse cohort
Diverticulitis is a common and morbid colorectal disease that recurs after an initial attack in up to 30% of patients. Elective surgery to remove the affected portion of the colon is an effective intervention to prevent disease recurrence, but appropriate patient selection is challenging given the limited ability to predict which patients are likely to recur, or the severity with which they may do so. Genetics influence diverticulitis and can be used for risk stratification, but this has only been studied in European ancestry populations. Using state-of-the-art techniques, we created a polygenic risk score that associates with diverticulitis prevalence and severity and is externally validated on meta-analysis in a diverse patient population across three different biobanks. This work represents the first published diverticulitis polygenic score to demonstrate utility in associating specifically with diverticulitis in non-European populations, and may provide the basis for clinical implementation in elective surgical decision-making.
Authors
- Noah L. Tsao (ORCID: https://orcid.org/0000-0002-5743-0795)
- Christopher J. Neylan (ORCID: https://orcid.org/0000-0002-6458-4485)
- John DePaolo (ORCID: https://orcid.org/0000-0002-6829-2594)
- Lillias H. Maguire (ORCID: https://orcid.org/0000-0002-6041-2416)
- Diane T. Smelser (ORCID: https://orcid.org/0000-0002-3925-8864)
- Sarah Abramowitz (ORCID: https://orcid.org/0000-0001-5515-1752)
- Jeffrey L. Roberson (ORCID: https://orcid.org/0000-0002-0168-8578)
- Alexander T. Hawkins (ORCID: https://orcid.org/0000-0002-8531-7247)
- David J. Carey (ORCID: https://orcid.org/0000-0001-6404-1950)
- Michael G. Levin (ORCID: https://orcid.org/0000-0002-9937-9932)
- Rebecca L. Hoffman (ORCID: https://orcid.org/0000-0002-7924-3544)
- Scott M. Damrauer (ORCID: https://orcid.org/0000-0001-8009-1632)
- Thomas E. Ueland (ORCID: https://orcid.org/0000-0001-6618-9318)
Institutions
- Geisinger Medical Center (US)
- Vanderbilt University (US)
- Hospital of the University of Pennsylvania (US)
- Donald & Barbara Zucker School of Medicine at Hofstra/Northwell (US)
- Philadelphia VA Medical Center (US)
- Geisinger Health System (US)
- Geisinger Commonwealth School of Medicine (US)
- University of Pennsylvania (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-11-27
- DOI
- https://doi.org/10.1038/s41598-025-26455-6
- Primary Topic
- Diverticular Disease and Complications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Veterans Affairs
- American Heart Association
- University of Pennsylvania
- Institute for Translational Medicine and Therapeutics
- Sarnoff Cardiovascular Research Foundation
- National Institutes of Health
- Perelman School of Medicine, University of Pennsylvania
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Center for Advancing Translational Sciences