A Journey through Genetic Architecture and Predisposition of Coronary Artery Disease

• Published in: Current genomics Vol. 21; no. 5; pp. 382 - 398
• Main Authors: Roberts, Robert, Chang, Chih Chao
• Format: Journal Article
• Language: English
• Published: United Arab Emirates Bentham Science Publishers Ltd 01.08.2020; Benham Science Publishers; Bentham Science Publishers
• Subjects: Cardiovascular disease; Chemotherapy; Clinical trials; Coronary artery; Coronary artery disease; Coronary vessels; Drug therapy; Genome-wide association studies; Genomes; Health risk assessment; Heart; Heart diseases; Prevention; Reduction; Risk analysis; Risk factors; coronary artery disease; Genome-wide association studies; genetic risk stratification; genetics; genomic; genetic risk variants; prevention; primary
• ISSN: 1389-2029; 1875-5488
• DOI: 10.2174/1389202921999200630145241

Introduction: To halt the spread of coronary artery disease (CAD), the number one killer in the world, requires primary prevention. Fifty percent of all Americans are expected to experience a cardiac event; the challenge is identifying those at risk. 40 to 60% of predisposition to CAD is genetic. The first genetic risk variant, 9p21, was discovered in 2007. Genome-Wide Association Studies has since discovered hundreds of genetic risk variants. The genetic burden for CAD can be expressed as a single number, Genetic Risk Score (GRS). Assessment of GRS to risk stratify for CAD was superior to conventional risk factors in several large clinical trials assessing statin therapy, and more recently in a population of nearly 500,000 (UK Biobank). Studies were performed based on prospective genetic risk stratification for CAD. These studies showed that a favorable lifestyle was associated with a 46% reduction in cardiac events and programmed exercise, a 50% reduction in cardiac events. Genetic risk score is superior to conventional risk factors, and is markedly attenuated by lifestyle changes and drug therapy. Genetic risk can be determined at birth or any time thereafter. Conclusion: Utilizing the GRS to risk stratify young, asymptomatic individuals could provide a paradigm shift in the primary prevention of CAD and significantly halt its spread.