Association of Genome-Wide Polygenic Risk Score for Body Mass Index with Cardiometabolic Health from Childhood Through Midlife

Abstract

Background: Genetic information may help to identify individuals in childhood who are at increased risk for cardiometabolic disease. Methods: We included 1201 BHS (Bogalusa Heart Study) participants (832 White participants and 369 Black participants) who were followed up to 42.3 years, starting at a mean age of 9.8 years. A validated genome-wide polygenic risk score (PRS) was tested for association with midlife body mass index (BMI), fasting plasma glucose, and systolic blood pressure using multiple linear regression models. Cox proportional hazards models tested associations of the PRS with incident obesity, diabetes, and hypertension. All analyses were conducted according to race and adjusted for baseline age, sex, ancestry, and BMI. Results: The constructed PRS was significantly and modestly correlated with midlife BMI in both White and Black participants, with correlation coefficients of 0.27 (P=1.94×10-8) and 0.16 (P=5.50×10-3), respectively. In White participants, per SD increase of PRS was associated with an average 1.29 kg/m2higher BMI (P=4.44×10-9), 2.82 mg/dL higher fasting plasma glucose (P=1.17×10-3), and 1.09 mm Hg higher systolic blood pressure (P=3.57×10-2) at midlife. The PRS also conferred a 26% higher increased risk of obesity (P=3.50×10-6) in White participants. In addition, the variance in midlife BMI explained increased from 0.1973 to 0.2293 when PRS was added to the model including age, sex, principal components, and baseline BMI (P<0.0001). No associations were observed in Black participants. Conclusions: Adiposity-related genetic information independently predicted cardiometabolic health in White BHS participants. Null associations observed in Black BHS participants highlight the urgent need for PRS development in multi-ancestry populations.