Genetic Risk, Healthy Lifestyle, and Risk Stratification for Diverticulitis

Area of Science:

• Gastroenterology
• Genetics
• Preventive Medicine

Background:

• A polygenic risk score (PRS) estimates genetic susceptibility to disease.
• The Life's Essential 8 (LE8) score assesses adherence to a healthy lifestyle.
• This study investigates the combined utility of PRS and LE8 in severe diverticulitis risk stratification.

Purpose of the Study:

• To evaluate the independent and combined predictive power of genetic risk and lifestyle factors for severe diverticulitis.
• To determine if a polygenic risk score complements lifestyle information for improved risk assessment.
• To develop and validate a disease-specific lifestyle score for diverticulitis.

Main Methods:

• A PRS for severe diverticulitis was developed and validated in BioVU, then applied to the UK Biobank cohort.
• The Life's Essential 8 (LE8) score, encompassing diet, exercise, smoking, sleep, weight, cholesterol, blood sugar, and blood pressure, was calculated.
• Cox proportional hazards models and relative excess risk due to interaction (RERI) were used to assess risk and interactions.

Main Results:

• In 225,592 UK Biobank participants, 2,584 developed severe diverticulitis over 14 years.
• Individuals with high genetic and lifestyle risk had a 4.71-fold increased hazard of severe diverticulitis (p < 0.01).
• The combined effect of genetic and lifestyle risk exceeded the sum of individual risks (RERI = 0.98).

Conclusions:

• Both polygenic risk scores and lifestyle scores are independently associated with severe diverticulitis.
• Integrating genetic and lifestyle data provides additive risk information beyond individual assessments.
• Personalized risk profiles incorporating genetics and lifestyle may aid shared decision-making regarding interventions.