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/m2 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 Conclusions While maintenance of a healthy body weight reduces gallstone disease risk among all individuals, risk reduction is higher among the subset with greater genetic susceptibility to gallstone disease.