Polygenic risk scores for coronary artery disease capture 10.8% to 33.1% of benchmark patients in early-onset CAD cohort.

This observational cohort study evaluated polygenic risk scores (PRSs) for coronary artery disease in 1,184 early-onset patients (<55 years) with a clinical profile of low 10-year risk and no diabetes or severe hypercholesterolemia. The study compared PRSs to established non-genetic biomarkers, such as lipoprotein(a), to identify a benchmark patient group.

The primary outcome was the proportion of benchmark patients captured by 58 CAD PRSs, which varied from 10.8% to 33.1%. The top-performing PRS was 2-fold more effective at identifying the benchmark group compared to non-genetic biomarkers. Secondary analysis showed that the lipid profiles of benchmark patients never captured by any score were significantly healthier.

Safety and tolerability were not reported, as no adverse events, serious adverse events, or discontinuations were documented. Key limitations include the observational design, which precludes causal inference, and the lack of reported funding or conflicts of interest.

The practice relevance is a framework for validating the clinical readiness of PRSs. Given the observational nature, these results suggest an association but do not confirm that PRSs improve individual-level risk prediction.