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Polygenic Risk Scores Highlight Potential for Developing Coronary Artery Disease

By LabMedica International staff writers
Posted on 09 Jun 2020
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Image: Micrograph of a coronary artery with the most common form of coronary artery disease (atherosclerosis) and marked luminal narrowing (Photo courtesy of Wikimedia Commons)
Image: Micrograph of a coronary artery with the most common form of coronary artery disease (atherosclerosis) and marked luminal narrowing (Photo courtesy of Wikimedia Commons)
By combining a polygenic risk score with results of more traditional clinical tests, it was possible to identify individuals at high-risk for development of coronary artery disease (CAD) who had not been recognized through standard clinical evaluations alone.

Polygenic risk scores (PRS) for CAD have been shown to identify high-risk individuals more likely to benefit from primary prevention statin therapy. How polygenic CAD risk related to traditional cardiovascular risk factors remained unclear.

Polygenic risk scores reflect a mathematical aggregate of risk conferred by many DNA variants to estimate the likelihood of a specific outcome, such as disease onset in an individual. The scores are the output of statistical models developed using data from large genome-wide association studies (GWAS).

For this study, investigators at Massachusetts General Hospital (Boston, USA) and the Broad Institute of Massachusetts Institute of Technology and Harvard University (Cambridge, USA) applied PRS to 47,108 individuals (11,020 or 23.4% with CAD). who were an average of 60 years old and were receiving care across three health care systems in the United States.

Results revealed that PRS strongly associated with the presence of coronary artery disease. Specifically, individuals with scores in the top 20% were 1.9-times more likely to have developed CAD compared with the remaining 80% of the population. However, those with high PRS were not more likely than others to have been previously recognized as high risk by their primary care physicians.

"We identified a subset of individuals at double the risk of heart attack on the basis of their genes. Despite this elevated risk, these individuals were neither more likely to be flagged as high risk, nor more likely to receive preventive statin therapy per our conventional clinical practices--a consistent finding across all three health systems studied," said first author Dr. Krishna Aragam, a cardiologist at Massachusetts General Hospital. "When coupled with clinical assessments, we estimate that genetic testing may uniquely identify a need for preventive statin therapy in approximately one in every 25 of such patients. Within our present frameworks for heart attack prevention, we speculate that genetic testing may be most immediately useful to guide clinical management for patients otherwise falling in a “gray area” of intermediate risk based on standard clinical factors."

The CAD study was published in the June 9, 2020, online issue of the Journal of the American College of Cardiology.

Related Links:
Massachusetts General Hospital
Broad Institute of Massachusetts Institute of Technology and Harvard University




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