Integrated polygenic risk scores (PRS) can estimate the risk for eight cardiovascular conditions, according to a study published online April 29 in the Journal of the American College of Cardiology.
Anika Misra, from the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, and colleagues analyzed genotype and clinical data from 245,394 All of Us Research Program participants to develop and validate integrated PRS for eight cardiovascular conditions. An elastic-net approach (PRSmix) was used to combine publicly available PRS for eight traits: coronary artery disease, atrial fibrillation, type 2 diabetes, venous thromboembolism (VTE), thoracic aortic aneurysm (TAA), extreme hypertension, severe hypercholesterolemia, and elevated lipoprotein(a).
The researchers found that integrated PRS demonstrated robust discrimination and appropriate calibration across the eight cardiovascular traits among 53,306 genotyped participants.
Comparing high genetic risk versus average risk yielded odds ratios of 3.7 for coronary artery disease, 3.1 for type 2 diabetes, 3.0 for atrial fibrillation, 1.9 for VTE, 1.7 for TAA, 2.1 for hypertension, 4.1 for hypercholesterolemia, and 41.0 for lipoprotein(a). Risk classification was improved by incorporating integrated PRS into clinical models, while significant associations with incident cardiovascular outcomes were confirmed in prospective analyses.
“Our goal is to provide clinicians and patients with actionable, understandable information about their genetic risk for common cardiovascular diseases,” co-senior author Aniruddh Patel, M.D., from Mass General Brigham Heart and Vascular Institute, said in a statement. “The tool already provides meaningful insight into cardiovascular risk, and we plan to continuously refine it as new genetic evidence emerges.”
Several authors disclosed ties to the biopharmaceutical industry.
Black Americans have a higher burden of hypertension, stroke, heart failure, and diabetes. Additionally, they often experience an earlier onset and greater disease severity. For clinicians, improving early risk stratification in historically underserved populations can help mitigate health inequities. By identifying hidden cardiovascular risks before they cause irreversible damage, providers can deliver more targeted preventive care — ultimately lowering healthcare costs and reducing premature mortality among Black patients.
Many polygenic risk scores are still disproportionately derived from European ancestry datasets, limiting relevance for patients of color. This leads to reduced predictive accuracy in African ancestry populations and increases the risk of underestimating or overestimating disease burden in Black patients.
Equitable genomic representation is critical in cardiology research, particularly when communities disproportionately affected by these conditions aren’t involved.
The “All of Us” dataset included a substantial number of participants of African ancestry, helping improve representation in genomic research. The team specifically evaluated calibration across ancestry groups, offering an opportunity to improve future models with more diverse genomic data.
Polygenic risk scores could support earlier preventive interventions for patients at high risk of developing cardiovascular disease. However, it shouldn’t be seen as a replacement for traditional risk factors — such as physical inactivity, heavy alcohol consumption, high cholesterol, and high blood pressure — but rather a supplemental tool.
Aside from genetics, it’s critical that providers are aware of the social determinants of health that can influence a patient’s outcomes. For Black patients, social factors like food deserts, chronic exposure to racial discrimination, and barriers to quality healthcare drive disparities in cardiovascular disease.
While PRS may improve early detection of cardiovascular risk, access and equity issues remain. Genetic testing can still be costly or difficult to access in underserved communities, potentially limiting its benefit for many Black patients.
In addition, there are concerns about medical mistrust, privacy, and the potential misuse of genetic data. Clinicians must approach these conversations with patients carefully and deliver culturally responsive counseling that explains both the benefits and limitations of PRS.
Genetics alone do not determine cardiovascular outcomes. Even among patients with elevated genetic risk, healthy lifestyle changes such as improved diet, exercise, smoking cessation, and blood pressure management can still significantly reduce cardiovascular risk.
Clinicians can use polygenic risk scores as a motivational tool rather than a fatalistic one, helping patients understand that prevention and early intervention still matter.
Researchers say more Black participation in genetic research and biobanks will be critical to improving the accuracy of PRS for African ancestry populations. Additional validation studies are necessary before these tools are widely adopted in clinical practice.
Experts emphasize combining genetic risk assessment with community-based prevention efforts to ensure precision medicine benefits all patient populations equitably.
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