Associations of cardiometabolic polygenic risk scores with cardiovascular disease in African Americans

Abstract

Background: Cardiovascular disease (CVD) is a complex disease, and genetic factors contribute individually or cumulatively to CVD risk. While African American women and men are disproportionately affected by CVD, their lack of representation in genomic investigations may widen disparities in health. We investigated the associations of cardiometabolic polygenic risk scores (PRSs) with CVD risk in African Americans. Methods: We used the Jackson Heart Study, a prospective cohort study of CVD in African American adults and the predicted atherosclerotic cardiovascular disease (ASCVD) 10-year risk. We included 40-79 years old adults without a history of coronary heart disease (CHD) or stroke at baseline. We derived genome-wide PRSs for systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, LDL cholesterol, hemoglobin A1c (HbA1c), triglycerides, and C-reactive protein (CRP) separately for each of the participants, using African-origin UK Biobank participants’ genome-wide association summary statistics. We estimated the associations between PRSs and 10-year predicted ASCVD risk adjusting for age, sex, study visit date, and genetic ancestry using linear and logistic regression models. Results: Participants (n=2,077) were 63% female and 66% never-smokers. They had mean (SD) 56 (10) years of age, 127.8 (16.3) mmHg SBP, 76.3 (8.7) mmHg DBP, 200.4 (40.2) mg/dL total cholesterol, 51.7 (14.7) mg/dL HDL cholesterol, 127.2 (36.7) mg/dL LDL cholesterol, 6.0 (1.3) mmol/mol HbA1c, 108.9 (81.7) mg/dL triglycerides and 0.53 (1.1) CRP. Their median (interquartile range) predicted 10-year predicted ASCVD risk was 8.0 (4.0-15.0). Participants in the >75th percentile for HbA1c PRS had 1.42 percentage-point greater predicted 10-year ASCVD risk (1.42 [95% CI: 0.58-2.26]) and higher odds of ≥10% predicted 10-year ASCVD risk (OR: 1.46 [95% CI: 1.03-2.07]) compared with those in the <25th percentile for HbA1c PRS. Participants in the >75th percentile for SBP PRS had higher odds of ≥10% predicted 10-year ASCVD risk (OR: 1.52 [95% CI: 1.07-2.15]) compared with those in the <25th percentile for SBP PRS. Conclusion: Among 40-79 years old African Americans without CHD and stroke, higher PRSs for HbA1c and SBP were associated with CVD risk. PRSs may help stratify individuals based on their clinical risk factors for CVD early prevention and clinical management.