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

Area of Science:

• Cardiovascular disease epidemiology
• Genetics and personalized medicine
• Nutritional science

Background:

• The interplay between genetic predisposition (polygenic risk score - PRS) and lifestyle factors (diet quality, physical activity) on cardiovascular disease risk is not fully understood across different ancestries.
• Previous research indicates varying impacts of PRS on disease risk, but its interaction with lifestyle interventions remains an area needing clarification.

Purpose of the Study:

• To investigate whether high diet quality and physical activity modify the association between polygenic risk score (PRS) and atherosclerotic cardiovascular disease (ASCVD) risk in European Americans and African Americans.
• To identify potential molecular pathways influenced by PRS and lifestyle interventions.

Main Methods:

• Cross-sectional analysis of de-identified data from 1987-2010, including self-reported European Americans (n=6575) and African Americans (n=1606).
• Assessment of PRS levels, categorized into tertiles, and their association with ASCVD risk.
• Evaluation of the impact of high diet quality (DASH, Mediterranean, Southern diets) combined with physical activity on ASCVD risk within different PRS tertiles.

Main Results:

• A high-risk PRS significantly increased ASCVD risk in both ancestries, with a more pronounced effect in African Americans (RR=1.59) compared to European Americans (RR=1.15-1.18).
• High physical activity and diet combinations (DASH, Mediterranean) substantially reduced ASCVD risk in the highest PRS tertiles for both groups, particularly in African Americans (RR=0.87-0.82).
• Identified molecular pathways included fructose metabolism, obesity, insulin resistance, type 2 diabetes, Vitamin D, depression, aging, and cancer signaling.

Conclusions:

• High diet quality and physical activity can effectively counterbalance the increased ASCVD risk associated with high polygenic risk scores, especially in African Americans.
• Lifestyle interventions demonstrate significant potential for mitigating genetically influenced ASCVD risk across diverse ancestral populations.
• Further research into specific molecular pathways can inform targeted prevention strategies.