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.