Polygenic Risk Scores: Evidence for Clinical Impact and Cost-Effectiveness

Introduction
Polygenic risk scores (PRS) combine thousands of common genetic variants to estimate an individual’s inherited risk for complex diseases, from heart disease to cancer. As genomic testing technology evolves and costs decline, PRS are gaining traction as a tool for earlier risk identification and more tailored preventive care ( https://pmc.ncbi.nlm.nih.gov/articles/PMC12759097/). 

Why PRS Matters in Healthcare

PRS are derived by weighting DNA variants across the genome to calculate a single personalized risk estimate for a specific disease. Compared with single-gene testing, PRS capture much more of the genetic architecture behind complex traits, making them powerful tools for risk stratification (https://pmc.ncbi.nlm.nih.gov/articles/PMC12759097/). 

Research shows that adding PRS to standard clinical risk tools — such as those for cardiovascular disease — can more accurately identify high-risk individuals, regardless of ancestry. This can help clinicians intervene earlier with lifestyle changes or preventive therapies (https://www.genomics.com/newsroom/aha-2025-new-study-from-genomics-shows-polygenic-risk-scores-improve-the-accuracy-of-cardiovascular-disease-risk-prediction). 

Cost-Effectiveness: What the Evidence Says

Multiple economic evaluations suggest that integrating PRS into screening and prevention strategies has the potential to be cost-effective:

✔ In workplace health programs, adding a PRS for coronary artery disease improved precision in risk assessment and reduced overall costs while increasing quality-adjusted life years (QALYs) (https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2023.1139496/full).
✔ Systematic reviews indicate that incorporating PRS into organized screening programs (e.g., for cancer) modestly improves clinical effectiveness and enhances cost-effectiveness compared with traditional approaches (https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065%2824%2900006-3/fulltext).
✔ Population-level genomic screening that combines sequencing with PRS shows a high probability of cost-effectiveness under commonly accepted thresholds for health economic evaluations (https://pmc.ncbi.nlm.nih.gov/articles/PMC12805663). 

What This Means for Health Systems

The integration of PRS into mainstream clinical practice could help shift healthcare toward prevention and personalized care. While cost-effectiveness varies by disease and screening protocol, the growing evidence suggests that genomic risk-stratification tools like PRS are becoming economically viable as sequencing costs fall (https://pmc.ncbi.nlm.nih.gov/articles/PMC12759097/). 

Patients and providers alike may soon benefit from genetic risk predictions that not only inform individual care but also support health systems in allocating resources more efficiently.