Association of Genetic Variants Related to Combined Exposure to Higher Body Mass Index and Waist-to-Hip Ratio on Lifelong Cardiovascular Risk in UK Biobank

OBJECTIVE: This study examines the individual and combined association of body mass index (BMI) and 7 waist-to-hip ratio (WHR) with cardiovascular diseases (CVD) risk using genetic scores of the 8 obesity measurements as proxies. DESIGN: A 2×2 factorial analysis approach was applied, with participants divided into four groups of lifetime exposure to low BMI and WHR, high BMI, high WHR, and high BMI and WHR based on weighted genetic risk scores. The difference in CVD risk across groups was evaluated using multivariable logistic regression. SETTING: Cohort study. PARTICIPANTS: A total of 408,003 participants were included from the prospective observational UK Biobank study. RESULTS: A total of 58,429 of CVD events were recorded. Compared to the low BMI and WHR genetic scores group, higher BMI or higher WHR genetic scores were associated with an increase in CVD risk (high BMI: odds ratio (OR), 1.07; 95%CI, 1.04-1.10; high WHR: OR, 1.12; 95%CI, 1.09-1.16). A weak additive effect on CVD risk was found between BMI and WHR (high BMI and WHR: OR, 1.16; 95%CI, 1.12-1.19). Subgroup analysis showed similar patterns between different sex, age (