Ancestry Specific Polygenic Risk Score, Dietary Patterns, Physical Activity, and Cardiovascular Disease

ABSTRACT Background It is unknown whether the impact of high diet-quality and physical activity (PA) depends on the level of polygenic risk score (PRS) in different ancestries. Objective Determine the associations and interactions between high-risk PRSs, dietary patterns, and high PA with atherosclerotic cardiovascular disease (ASCVD) in European Americans (EAs) and African Americans (AAs). Another aim determined the molecular pathways of PRS-mapped genes and their relationships with dietary intake. Methods Cross-sectional analyses utilized de-identified data from 1987-2010 from 7-National Heart, Lung, and Blood Institute Candidate Gene Association Resource studies from the Database of Genotypes and Phenotypes studies for EAs (n=6,575) and AAs (n=1,606). Results The high-risk PRS increased ASCVD risk by 59% (Risk Ratio=1.59;95% Confidence Interval:1.16-2.17) in the highest tertile for AAs and by 15% (RR=1.15;1.13-1.30) and 18% (RR=1.18;1.04-1.35) in the second and highest tertiles compared to the lowest tertile in EAs. Within the highest PRS tertiles, high PA-diet combinations (Dietary Approaches to Stop High Blood Pressure (DASH), or Mediterranean, or Southern) reduced ASCVD risks by 9% (RR=0.91;0.85-0.96) to 15% (RR=0.85;0.80-0.90) in EAs; and by 13% (RR=0.87;0.78-0.97) and 18% (RR=0.82;0.72-0.95) for the DASH and Mediterranean diets, respectively in AAs. Top molecular pathways included fructose metabolism and catabolism linked to obesity, insulin resistance, and type 2 diabetes in both ancestries. Additional molecular pathways for AAs were Vitamin D linked to depression and aging acceleration; and death signaling associated with cancer. Conclusions Effects of high diet-quality and high PA can counterbalance the influences of genetically high-risk PRSs on ASCVD risk, especially in AAs.