Obesity, Adiposity, and Risk of Symptomatic Gallstone Disease According to Genetic Susceptibility

BACKGROUND & AIMS: Adiposity has been consistently associated with gallstone disease risk. We aimed to characterize associations of anthropometric measures (body mass index [BMI], recent weight change, long-term weight change, waist circumference, and waist-to-hip ratio) with symptomatic gallstone disease according to strata of gallstone disease polygenic risk score (PRS). METHODS: We conducted analysis among 34,626 participants with available genome-wide genetic data within 3 large, prospective, U.S. cohorts-the Nurses' Health Study (NHS), Health Professionals Follow-Up Study, and NHS II. We characterized joint associations of PRS and anthropometric measures and tested for interactions on the relative and absolute risk scales. RESULTS: Women in the highest BMI and PRS categories (BMI ≥30 kg/m(2) and PRS ≥1 SD above mean) had odds ratio for gallstone disease of 5.55 (95% confidence interval, 5.29 to 5.81) compared with those in the lowest BMI and PRS categories (BMI