Ancestry Specific Polygenic Risk Score, Dietary Patterns, Physical Activity and Incident Type 2 Diabetes

Area of Science:

• Genetics and Public Health
• Metabolic Disease Research
• Nutritional Epidemiology

Background:

• The interplay between genetic predisposition (polygenic risk score - PRS) and lifestyle factors in mitigating type 2 diabetes mellitus (T2DM) risk across diverse ancestries remains unclear.
• Investigating how lifestyle modifications can counteract genetically driven T2DM risk is crucial for personalized prevention strategies.

Purpose of the Study:

• To determine the associations and interactions between high-risk PRS, dietary patterns, physical activity, and metabolic burden on incident T2DM in European Americans and African Americans.
• To identify ancestry-specific PRS-mapped genes and associated molecular pathways.

Main Methods:

• Longitudinal study (1976-2015) using de-identified data from 8,283 European Americans and 1,205 African Americans from NHLBI Candidate Gene Association Resource studies.
• Analysis of associations and interactions using biased-corrected odds ratios (OR) and 95% confidence intervals (CI).

Main Results:

• African Americans exhibited a higher T2DM risk magnitude from high-risk PRS alone compared to European Americans.
• Protective effects against T2DM were observed with the Dietary Approaches to Stop High Blood Pressure (DASH) and Mediterranean diets.
• Interactions between diet, physical activity, and high-risk PRS/metabolic burden demonstrated attenuated T2DM risk, particularly with Mediterranean and DASH diets.

Conclusions:

• Individuals with the highest PRS and metabolic burden may benefit from early intervention to reduce T2DM risk.
• Clinicians should recommend DASH and Mediterranean diets combined with physical activity for T2DM prevention and management.
• Dietary interventions show potential for reversing detrimental molecular pathways and mitigating T2DM progression.