GWAS breakthroughs: mapping the journey from one locus to 393 significant coronary artery disease associations

Cardiovasc Res. 2024 Nov 5;120(13):1508-1530. doi: 10.1093/cvr/cvae161.

Abstract

Coronary artery disease (CAD) poses a substantial threat to global health, leading to significant morbidity and mortality worldwide. It has a significant genetic component that has been studied through genome-wide association studies (GWAS) over the past 17 years. These studies have made progress with larger sample sizes, diverse ancestral backgrounds, and the discovery of multiple genomic regions related to CAD risk. In this review, we provide a comprehensive overview of CAD GWAS, including information about the genetic makeup of the disease and the importance of ethnic diversity in these studies. We also discuss challenges of identifying causal genes and variants within GWAS loci with a focus on non-coding regions. Additionally, we highlight tissues and cell types relevant to CAD, and discuss clinical implications of GWAS findings including polygenic risk scores, sex-specific differences in CAD genetics, ethnical aspects of personalized interventions, and GWAS guided drug development.

Keywords: Atherosclerosis; Coronary artery disease; Genetics; Genome-wide association studies; Post-GWAS.

Publication types

  • Review

MeSH terms

  • Coronary Artery Disease* / genetics
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Multifactorial Inheritance
  • Phenotype*
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Sex Factors