Author: Dr Fouad Bitar

The editorial highlights that the PROACT study introduces a novel genome-first strategy using polygenic
risk scores (PRS) to identify individuals who appear low-risk by traditional calculators but frequently
harbor subclinical coronary artery disease. It argues that prevention must evolve beyond age-based risk
models toward earlier, causal-factor–guided intervention integrating genomics, imaging, and targeted
therapy. 

This Landmark JAMA 2026 PROACT trials showed that adults with high coronary artery disease (CAD)
polygenic risk scores but low clinical risk were prospectively identified from a biobank and evaluated
with coronary CT angiography, demonstrating that about half had previously undetected subclinical
plaque despite favorable cardiovascular health. These findings show the feasibility of genome-first
prevention strategies and suggest that polygenic risk–guided identification could enable earlier targeted
pharmacologic prevention in individuals overlooked by conventional risk models. 

This NEJM 2026 review supports DNA-based population screening with PRS as a key tool for
risk-stratified prevention allowing targeted, earlier interventions.

This NEJM 2026 review shows that CAD polygenic risk scores (PRS) identify a high-risk group, often missed by traditional calculators and meaningfully improve risk prediction and provide absolute benefit is greatest in high-PRS individuals.

This landmark JAMA 2025 trial showed that PRS-powered risk-based breast cancer screening was non-inferior to annual screening and was associated with an approximately one-third lower rate of advanced cancer.
This landmark JAMA 2025 WISDOM trial showed that PRS-powered risk-based breast cancer screening was non-inferior to annual screening and was associated with an approximately one-third lower rate of advanced (stage ≥IIB) cancers (30.0 vs 48.0 per 100,000 person-years), with nearly doubled uptake of preventive therapy among the highest-risk women, establishing PRS-guided screening as a scalable and clinically sound strategy.

This landmark NEJM 2025 study showed that PRS-guided screening of men in the top genetic risk decile substantially improves detection of clinically significant prostate cancer, uncovering many high-risk cancers missed by standard PSA pathways, and establishes PRS-based risk stratification as a scalable, clinically impactful screening strategy.