ArticleJournal of the American College of Cardiology2026
Development and Validation of a Clinical Polygenic Risk Report in U.S.-Based Health Systems for 8 Cardiovascular Conditions.
Article in Journal of the American College of Cardiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Performance of Cardiovascular Polygenic Risk Scores in Carotid Stenosis Identification.medRxiv : the preprint server for health sciences · 2026Article
- Precision cardiovascular-kidney-metabolic care - ready for prime time? A fellow's voice.American journal of preventive cardiology · 2026Article
- The predictive value of combined assessment of estimated glucose disposal rate and non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio for cardiovascular disease risk: a nationwide cohort study.Frontiers in medicine · 2026Article
- Genetic Causes of Thoracic Aortic Aneurysm: A Review.Methodist DeBakey cardiovascular journal · 2026Review
- Polygenic risk score translation across diverse populations.Frontiers in cardiovascular medicine · 2026Review
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
backgroundPolygenic risk scores (PRS) stratify inherited cardiovascular risk, but their path to clinical implementation remains unclear.
objectivesWe aimed to develop and validate integrated PRS for 8 cardiovascular conditions and outline a framework for their clinical reporting.
methodsWe analyzed genotype and clinical data from 245,394 All of Us Research Program participants. Publicly available PRS for 8 traits-coronary artery disease, atrial fibrillation, type 2 diabetes, venous thromboembolism (VTE), thoracic aortic aneurysm (TAA), extreme hypertension, severe hypercholesterolemia, and elevated lipoprotein(a)-were combined using PRSmix, an elastic-net approach. Integrated PRS were externally validated in 53,306 Mass General Brigham Biobank participants using logistic regression, adjusting for age, sex, and ancestry.
resultsOf 53,306 genotyped Mass General Brigham Biobank participants (55.6% women, mean age 53 ± 17 years), integrated PRS demonstrated robust discrimination and appropriate calibration across 8 cardiovascular traits. Comparing high genetic risk (top 10% of PRS distribution, or top 20% for rarer TAA and VTE) vs average risk (26th-75th percentiles, or 21st-80th percentiles for TAA and VTE) yielded ORs: coronary artery disease (3.7 [95% CI: 3.4-4.1]), type 2 diabetes (3.1 [95% CI: 2.8-3.3]), atrial fibrillation (3.0 [95% CI: 2.7-3.3]), VTE (1.9 [95% CI: 1.6-2.0]), TAA (1.7 [95% CI: 1.5-1.9]), hypertension (2.1 [95% CI: 1.8-2.3]), hypercholesterolemia (4.1 [95% CI: 3.7-4.5]), and lipoprotein(a) (41.0 [95% CI: 27.0-62.2]). Incorporating integrated PRS into clinical models improved risk classification, while prospective analyses confirmed significant associations with incident cardiovascular outcomes.
conclusionsIntegrated PRS offer an implementable framework for genetic risk reporting, and are now available as a clinically orderable test. Broader prospective validation studies are needed to further establish clinical utility.
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