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

It is unknown whether the impact of high diet quality and physical activity depends on the level of polygenic risk score (PRS) in different ancestries. Our cross-sectional study utilized de-identified data from 1987-2010 for self-reported European Americans (n = 6575) and African Americans (n = 1606). The high-risk PRS increased ASCVD risk by 59% (Risk Ratio (RR) = 1.59; 95% Confidence Interval:1.16-2.17) in the highest tertile for African Americans 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 European Americans. Within the highest PRS tertiles, high physical activity-diet combinations (Dietary Approaches to Stop High Blood Pressure (DASH), 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 European Americans; and by 13% (RR = 0.87; 0.78-0.97) and 18% (RR = 0.82; 0.72-0.95) for DASH and Mediterranean diets, respectively, in African Americans. Top molecular pathways included fructose metabolism and catabolism linked to obesity, insulin resistance, and type 2 diabetes. Additional molecular pathways for African Americans were Vitamin D linked to depression and aging acceleration and death signaling associated with cancer. Effects of high diet quality and high physical activity can counterbalance the influences of genetically high-risk PRSs on ASCVD risk, especially in African Americans.