Development of a Polygenic Risk Score to Predict Diverticulitis

BACKGROUND: Despite its prevalence and associated morbidity, we remain limited in our ability to predict the course of a patient with diverticular disease. While several clinical and genetic risk factors have been identified, we do not know how these factors relate to one another. OBJECTIVE: To determine if a polygenic risk score could improve risk prediction for diverticulitis and recurrent diverticulitis compared to a model using only clinical factors. DESIGN: An observational study. SETTING: Study examines the predictive ability of a polygenic risk score for diverticulitis developed using prior genome wide association studies and validated using the MyCode biobank. PATIENTS: Patients of European ancestry in the Geisinger Health System who were enrolled in the MyCode Community Health biobanking program. MAIN OUTCOME MEASURES: The ability of a polygenic risk score to predict diverticulosis, diverticulitis, and recurrent diverticulitis. RESULTS: A total of 60,861 patients were included, of which 9,912 (16.3%) had diverticulosis or diverticulitis (5,015 with diverticulosis and 4,897 with diverticulitis). When divided into deciles, our polygenic risk score stratified patients by risk of both diverticulosis and diverticulitis with a 2-fold difference in disease risk between the highest and lowest deciles for diverticulitis and a 4.8-fold difference for recurrent complicated diverticulitis. When compared to clinical factors alone, our polygenic risk score was able to improve risk prediction of recurrent diverticulitis. LIMITATIONS: Our population is largely located in a single geographic region and were classified by disease status using international classification of diseases codes. CONCLUSIONS: This predictive model stratifies patients based on genetic risk for diverticular disease. The increased frequency of recurrent disease in our high-risk patients suggests that a polygenic risk score, in addition to other factors, may help to guide the discussion regarding surgical intervention.