Validated polygenic risk, calibrated across ancestries.
ARC-OMIX coronary heart disease scores are validated in two ancestrally varied U.S. cohorts that include European-, African-, and Hispanic/Latino-ancestry participants. Validation for the other ARC-PREVENT conditions is in progress.
Polygenic risk and family history are independently and additively informative.
The C-statistic of the Pooled Cohort Equations rises from 0.719 to 0.753 when polygenic risk and family history are added together.
Net benefit: ~4 additional true positives per 1,000 screened at the 7.5% threshold. In adults <40 yr, c-statistic rises from 0.757 to 0.827.
PRS and family history capture partially non-overlapping genetic risk. A patient with both carries nearly 4× the baseline risk — a signal that standard clinical assessments miss.
Top 5% PRS threshold. Cox proportional hazards model adjusted for age, sex, 5 PCs; 95% CIs shown.
Trained and validated across large, ancestrally varied populations.
MI-GENES: ten years of follow-up.
In the MI-GENES randomized trial, adults at intermediate coronary risk whose risk estimate included a polygenic risk score started statins more often and had lower LDL cholesterol at six months than those given a conventional score alone. In a post hoc ten-year follow-up (Naderian et al., Circulation: Genomic and Precision Medicine, 2025; listed under Publications below), the polygenic-risk group had fewer major adverse cardiovascular events: 2 versus 9 (hazard ratio 0.20, 95% CI 0.04–0.94). The trial was small (n=203), so the estimate is imprecise, but it suggests genetic risk information can support durable clinical decisions, not just a one-time result.
Publications
2026
Clinical use of polygenic risk scores: current status, barriers and future directions
Nature Reviews Genetics · 2026
View on PubMed →2025
Effect of disclosing a polygenic risk score for coronary heart disease on adverse cardiovascular events
Circulation: Genomic and Precision Medicine · 2025
View on PubMed →2024
Associations of self-reported race, social determinants of health, and polygenic risk with coronary heart disease
Journal of the American College of Cardiology · 2024
View on PubMed →2022
2016
Incorporating a genetic risk score into coronary heart disease risk estimates: effect on LDL cholesterol levels
Circulation · 2016
View on PubMed →See how this evidence becomes a clinical report.
The scores and calibration methods above are what run inside every ARC-OMIX report — explore the platform, or see what clinicians receive.