Genetic Basis of Coronary Artery Disease: From GWAS Genome-Wide Association Studies to Precision Medicine

Abstract

Coronary artery disease (CAD) remains the leading cause of morbidity and mortality worldwide and results from a complex interplay of genetic and environmental factors (1, 2). Although traditional risk factors such as hypertension, diabetes mellitus, and dyslipidemia are well established, genetic predisposition significantly contributes to disease susceptibility and progression (1, 12). Advances in genome-wide association studies (GWAS)have identified numerous loci associated with CAD, implicating pathways related to lipid metabolism, inflammation, and vascular remodeling (3,13,14). Epigenetic mechanisms and gene-environment interactions further modulate disease expression and contribute to phenotypic variability (9, 22).
Polygenic risk scores (PRS), which integrate the cumulative effects of multiple genetic variants, have emerged as valuable tools for risk prediction and early identification of high-risk individuals (10, 16). However, despite these advances, challenges related to clinical implementation, population diversity, and ethical considerations remain significant barriers to translation into routine practice ( 24, 28,29). This review provides a comprehensive and critical overview of the genetic architecture of CAD and highlights the translational potential and limitations of precision medicine approaches in cardiovascular care.