Polygenic Risk Score Translation Across Diverse Populations

By
Krieger, Jose E
June 8, 2026
0 min

Frontiers In Cardiovascular Medicine

Overview

This review discusses the limitations of polygenic risk scores (PRSs) derived from predominantly European-ancestry datasets and their performance in diverse populations. It highlights recent advances in multi-ancestry PRS development, particularly for cardiovascular and cardiometabolic diseases, emphasizing the need for improved calibration and clinical utility across varied ancestry groups.

Background

Polygenic risk scores are increasingly recognized as valuable tools for risk stratification in diseases such as coronary artery disease, hypertension, and type 2 diabetes. However, the majority of existing PRSs are based on European-ancestry populations, leading to significant performance disparities in underrepresented and admixed populations. Addressing these disparities is crucial for the equitable application of precision medicine in diverse patient populations.

Data Highlights

No numerical data provided in the article.

Key Findings

PRSs derived from European-ancestry datasets show significantly lower predictive accuracy in non-European populations, with accuracy declines reported as high as 4.9-fold in African populations.
Recent methodological advances include the development of multi-ancestry PRSs that improve predictive performance across diverse populations.
Coronary artery disease (CAD) has the most mature PRS evidence, demonstrating clinically relevant gains from multi-ancestry approaches.
Methodological progress in blood pressure, hypertension, and type 2 diabetes is notable, but challenges remain in calibration and implementation.
Admixed populations should be viewed as essential contexts for developing robust PRS models rather than merely as settings where PRSs underperform.

Clinical Implications

Healthcare professionals should be aware of the limitations of current PRSs in diverse populations and consider the need for multi-ancestry models in clinical practice. The integration of ancestry-aware approaches may enhance risk stratification and improve patient outcomes in underrepresented groups.

Conclusion

The future of precision cardiovascular medicine hinges on the successful translation of polygenic risk scores across diverse populations, necessitating ongoing methodological advancements and careful implementation in clinical settings.