Genomic Risk Score Identifies Inherited Risk for Multiple Cardiovascular Conditions

Cardiovascular disease is the leading cause of death worldwide, yet many at‑risk individuals are overlooked by traditional calculators. Tools that weigh age, sex, blood pressure, and cholesterol can miss inherited predisposition detectable only through genomic analysis. The gap limits timely prevention and risk‑tailored interventions across common cardiometabolic conditions. Researchers now demonstrate a validated genomic tool that estimates inherited risk for eight common cardiovascular conditions.

Mass General Brigham Heart and Vascular Institute (Boston, MA, USA) and collaborators developed an integrated polygenic risk score (PRS) to quantify inherited risk across eight conditions: coronary artery disease, atrial fibrillation, type 2 diabetes, venous thromboembolism, thoracic aortic aneurysm, extreme hypertension, severe hypercholesterolemia, and elevated lipoprotein(a). The offering is currently available through the Mass General Brigham Laboratory for Molecular Medicine and Broad Clinical Labs. Results from the validation study are published in the Journal of the American College of Cardiology.

Image: The integrated polygenic risk score combines information from multiple genetic variants into a single test that provides a result for each of eight cardiovascular conditions (photo credit: Adobe Stock)

The PRS aggregates information from many genetic variants into a single test that yields a result for each condition. Investigators combined previously published genetic risk models from the Polygenic Score Catalog to produce a consolidated, more robust output. Patient‑facing reports classify genetic risk as high, average, or low, display how an individual compares with the general population, and are designed to integrate with electronic health records and patient portals.

Model development used genetic and health data from 245,000 participants in the National Institutes of Health All of Us Research Program. External validation was conducted in 53,000 patients from the Mass General Brigham Biobank. In the validation analysis, individuals in the top 10% of genetic risk were 3.7 times more likely to develop coronary artery disease than those at average risk, and those with the highest genetic risk for type 2 diabetes were 3.1 times more likely to develop the condition.

The authors note that additional studies are needed to define how best to incorporate genetic risk into clinical decision‑making. They also emphasize the importance of ensuring performance across diverse populations, as many scores in the Polygenic Score Catalog were derived largely from cohorts of European ancestry. The PRS is positioned to streamline interpretation for clinicians and patients while efforts continue to expand equity and refine the underlying evidence base.

"Most patients who are at increased genetic risk for serious heart conditions have no idea because their traditional risk factors appear relatively normal. Our goal is to provide clinicians and patients with actionable, understandable information about their genetic risk for common cardiovascular diseases," said co-senior author Aniruddh Patel, MD, a cardiologist and researcher with Mass General Brigham Heart and Vascular Institute who helped develop the tool.

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Mass General Brigham Heart and Vascular Institute