Researchers at Mass General Brigham Heart and Vascular Institute and collaborators have validated a new integrated polygenic risk score (PRS) tool designed to estimate inherited risk for eight common cardiovascular and metabolic conditions, potentially expanding opportunities for earlier intervention and prevention.
The validation study, published in the Journal of the American College of Cardiology, evaluated how effectively the DNA-based test could stratify patients according to genetic susceptibility for diseases that are often identified only after traditional clinical risk factors become apparent.
The PRS test is currently available through the Mass General Brigham Laboratory for Molecular Medicine and Broad Clinical Labs.
Expanding cardiovascular risk assessment
Cardiovascular disease remains the leading cause of death worldwide, and conventional risk assessment methods—including age, sex, cholesterol levels, and blood pressure—do not always capture inherited disease susceptibility. According to the researchers, polygenic risk scoring could help identify patients who may benefit from earlier monitoring, lifestyle interventions, or preventive therapies despite otherwise normal clinical profiles.
The integrated PRS test evaluates genetic risk for coronary artery disease, atrial fibrillation, type 2 diabetes, venous thromboembolism, thoracic aortic aneurysm, extreme hypertension, severe hypercholesterolemia, and elevated lipoprotein(a).
To develop the tool, investigators combined previously published genetic risk models from the Polygenic Score Catalog into a unified testing platform. The system was trained using genomic and clinical data from 245,000 participants enrolled in the National Institutes of Health’s All of Us Research Program and validated in 53,000 patients from the Mass General Brigham Biobank.
Individuals whose scores ranked in the top 10% for coronary artery disease risk were 3.7 times more likely to develop the condition compared to individuals with average genetic risk. Patients in the highest genetic risk category for type 2 diabetes were 3.1 times more likely to develop disease than those with average scores.
Designed for clinical use
In addition to categorizing risk as high, average, or low, the report includes explanations of each condition and visual graphs comparing a patient’s genetic risk with that of the broader population. The PRS report can also be integrated into electronic health records and patient portals to support clinical workflows.
“Interpreting DNA risk is new for the public as well as clinicians,” said co-senior author Pradeep Natarajan, director of Preventive Cardiology at Mass General Brigham Heart and Vascular Institute. “It was very important to us to provide a clear genetic risk report that would be accessible and patient-friendly.”
The researchers cautioned that additional studies are needed to determine how polygenic risk information should be incorporated into clinical decision-making and to further evaluate performance across diverse populations, as many existing genetic risk models have been derived primarily from individuals of European ancestry.
“Most patients who are at increased genetic risk for serious heart conditions have no idea because their traditional risk factors appear relatively normal,” said co-senior author Aniruddh Patel. “The tool already provides meaningful insight into cardiovascular risk, and we plan to continuously refine it as new genetic evidence emerges.”
Note: This news summary was generated by AI based on a published press release, followed by a review from human editors.
