Prevention & lipidsDiagnostic or prognostic study
Development and Validation of a Clinical Polygenic Risk Report in U.S.-Based Health Systems for 8 Cardiovascular Conditions
- Development and validation study of polygenic risk scores
- external validation
Authors' conclusion
Integrated PRS offer an implementable framework for genetic risk reporting, and are now available as a clinically orderable test.
Study context
- Population
- All of Us Research Program participants (development); Mass General Brigham Biobank participants (external validation; 55.6% women, mean age 53 ± 17 years)validation
- Participants
- 53,306 participants
- Comparison
- High genetic risk vs average risk
Performance
As reported in the abstract
Association of high vs average integrated PRS with 8 CV traits
High genetic risk vs Average riskOdds ratio (95% CI)
CAD
3.7(3.4–4.1)
T2DM
3.1(2.8–3.3)
AF
3.0(2.7–3.3)
VTE
1.9(1.6–2.0)
TAA
1.7(1.5–1.9)
hypertension
2.1(1.8–2.3)
hypercholesterolemia
4.1(3.7–4.5)
lipoprotein(a)
41.0(27.0–62.2)
Further findings
Discrimination and calibration
- Robust discrimination and appropriate calibration across 8 CV traits
Risk classification and incident CV outcomes
- Adding integrated polygenic risk scores (PRS) to clinical models improved risk classification
- Prospective analyses confirmed significant associations with incident CV outcomes
Original publication
Development and Validation of a Clinical Polygenic Risk Report in U.S.-Based Health Systems for 8 Cardiovascular Conditions. J Am Coll Cardiol. Published 29 April 2026. doi:10.1016/j.jacc.2026.03.035
Summarised from the published abstract; every number is checked against it