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

Area of Science:

• Genetics and Cardiovascular Health
• Nutritional Science
• Public Health

Background:

• Investigating the interplay between genetic predisposition (polygenic risk score - PRS), lifestyle factors (diet quality, physical activity - PA), and atherosclerotic cardiovascular disease (ASCVD) risk across different ancestries.
• Understanding whether the protective effects of healthy lifestyle choices are modified by PRS levels and ancestry.

Approach:

• Utilizing cross-sectional data from 7 National Heart, Lung, and Blood Institute studies (1987-2010) including European Americans (EAs, n=6,575) and African Americans (AAs, n=1,606).
• Analyzing associations and interactions between high-risk PRS, dietary patterns (DASH, Mediterranean, Southern), and high PA with ASCVD risk.
• Exploring molecular pathways associated with PRS-mapped genes and their relationship with dietary intake.

Key Points:

• High-risk PRS significantly increased ASCVD risk in both EAs and AAs, with a more pronounced effect in AAs.
• Combined high-quality diet and high PA interventions notably reduced ASCVD risk within the highest PRS tertiles for both ancestries.
• Specific dietary patterns (DASH, Mediterranean) showed significant risk reduction in AAs.
• Identified molecular pathways linked PRS to metabolic dysfunction (obesity, insulin resistance, type 2 diabetes), and in AAs, to Vitamin D-related issues and cancer signaling.

Conclusions:

• High-quality diet and physical activity can effectively mitigate the increased ASCVD risk associated with high polygenic risk scores.
• Lifestyle interventions demonstrate a particularly strong counterbalance effect against genetic predisposition in African Americans.
• Findings highlight the importance of personalized lifestyle recommendations considering genetic risk and ancestry.