Development of a Polygenic Risk Score to Predict Diverticulitis

Area of Science:

• Gastroenterology
• Genetics
• Predictive Modeling

Background:

• Diverticular disease poses significant morbidity, yet predicting patient outcomes remains challenging.
• Existing clinical and genetic risk factors lack clear interrelationships for comprehensive prediction.

Purpose of the Study:

• To evaluate if a polygenic risk score (PRS) enhances risk prediction for diverticulitis and recurrent diverticulitis compared to clinical factors alone.
• To assess the PRS's ability to stratify patients based on genetic predisposition to diverticular disease.

Main Methods:

• Observational study utilizing the MyCode Community Health biobank.
• Development and validation of a PRS for diverticulitis using genome-wide association studies.
• Inclusion of 60,861 patients of European ancestry from the Geisinger Health System.

Main Results:

• The PRS effectively stratified patients into risk deciles for diverticulosis and diverticulitis.
• A 2-fold difference in diverticulitis risk and a 4.8-fold difference in recurrent complicated diverticulitis risk were observed between the highest and lowest deciles.
• The PRS demonstrated improved risk prediction for recurrent diverticulitis over clinical factors alone.

Conclusions:

• A PRS can stratify individuals by genetic risk for diverticular disease.
• The PRS may assist in clinical decision-making, particularly regarding surgical intervention for high-risk patients with recurrent disease.