Unraveling the genetic blueprint of coronary artery disease: The role of polygenic risk scores in risk prediction

Cardiovascular diseases, and most notably coronary artery disease (CAD), carry a large burden of mortality and morbidity, highlighting the need for better risk prediction and prevention. Several risk scoring tools for CAD have been developed to improve early detection, reduce the risk of acute cardiac events, and ensure adequate monitoring and follow-up of high-risk individuals. One that seized attention, especially with the groundbreaking advancements in disease's genetic buildup, was the polygenic risk score (PRS) for CAD. It was developed for potentially improving risk prediction at an early age, with individualized patient care. Our review aims to review the latest advances in this field of polygenic risk prediction, highlighting background information about PRS, current evidence supporting the utility of PRS for CAD, challenges associated with its implementation, and its complementary role with the coronary artery calcium score (CAC). Our review demonstrates that PRS could be a strong predictive indicator of CAD, especially when combined with other clinical factors. However, concerns remain regarding its applicability to genetically diverse populations, the ethical and psychological challenges, and practical feasibility. Lastly, PRS can augment and predict CAC in terms of risk discrimination and reclassification. In conclusion, PRS is a valuable tool that is upscaling with wider adoption. This requires a proper handling of its associated challenges to better shape the future of individualized care.