Single-nucleotide polymorphisms in coronary artery disease: Biological complexity, risk architecture, and implications for precision prevention

Abstract

Coronary artery disease (CAD) is characterized by significant genetic diversity with interindividual genetic variation. Genomewide association studies have discovered many CAD-associated single-nucleotide polymorphisms (SNPs) and provided for the development of polygenic risk scores (PRS) to measure total genetic susceptibility. This review reviews the present evidence of SNPs in connection with CAD risk, discusses biological mechanisms whereby genetic variation affects vascular and metabolic phenotypes, and provides some methodological advances and limitations in PRS construction and testing. Although PRS extends risk stratification beyond clinical factors, its clinical utility is limited by population-level effects, limited biological interpretability, and variable predictive performance. Furthermore, we also discuss new approaches incorporating genetically informed risk assessment into clinical and imaging-based schemes to aid precision prevention. By explicitly bridging genetic association, biological interpretabilities, and clinical support, we aim to encourage responsible translation of genetic risk stratifying into CAD prevention.

Keywords

coronary artery disease / polygenic risk score / precision prevention / single-nucleotide polymorphism

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