A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Institute for Cardiogenetics, University of Lübeck, Marie-Curie-Str. Haus 67/BMF, 23562 Lübeck, Germany.
Cardiovasc Res. 2024 Nov 5;120(13):1508-1530. doi: 10.1093/cvr/cvae161.
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.
冠状动脉疾病 (CAD) 对全球健康构成重大威胁，导致全球发病率和死亡率显著上升。通过过去 17 年的全基因组关联研究 (GWAS)，已经对其遗传成分进行了深入研究。这些研究通过更大的样本量、更多元的祖先背景和发现与 CAD 风险相关的多个基因组区域取得了进展。在这篇综述中，我们全面概述了 CAD GWAS，包括疾病的遗传构成以及这些研究中种族多样性的重要性。我们还讨论了在 GWAS 位点中识别因果基因和变体的挑战，重点关注非编码区域。此外，我们还强调了与 CAD 相关的组织和细胞类型，并讨论了 GWAS 发现的临床意义，包括多基因风险评分、CAD 遗传学中的性别特异性差异、个性化干预的种族方面以及 GWAS 指导的药物开发。
