Purpose of the Review

Coronary artery disease (CAD) is a common disease globally attributable to the interplay of complex genetic and lifestyle factors. Here, we review how genomic sequencing advances have broadened the fundamental understanding of the monogenic and polygenic contributions to CAD and how these insights can be utilized, in part by creating polygenic risk estimates, for improved disease risk stratification at the individual patient level.

Recent Findings

Initial studies linking premature CAD with rare familial cases of elevated blood lipids highlighted high-risk monogenic contributions, predominantly presenting as familial hypercholesterolemia (FH). More commonly CAD genetic risk is a function of multiple, higher frequency variants each imparting lower magnitude of risk, which can be combined to form polygenic risk scores (PRS) conveying significant risk to individuals at the extremes. However, gaps remain in clinical validation of PRSs, most notably in non-European populations.

Summary

With improved and more broadly utilized genomic sequencing technologies, the genetic underpinnings of coronary artery disease are being unraveled. As a result, polygenic risk estimation is poised to become a widely used and powerful tool in the clinical setting. While the use of PRSs to augment current clinical risk stratification for optimization of cardiovascular disease risk by lifestyle change or therapeutic targeting is promising, we await adequately powered, prospective studies, demonstrating the clinical utility of polygenic risk estimation in practice.

中文翻译：

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冠状动脉疾病的单基因和多基因模型

审查目的

冠状动脉疾病 (CAD) 是一种全球常见的疾病，可归因于复杂的遗传和生活方式因素的相互作用。在这里，我们回顾了基因组测序的进步如何拓宽了对 CAD 的单基因和多基因贡献的基本理解，以及如何利用这些见解，部分通过创建多基因风险估计，以改善个体患者水平的疾病风险分层。

最近的发现

将早发 CAD 与罕见的家族性血脂升高病例联系起来的初步研究强调了高风险的单基因贡献，主要表现为家族性高胆固醇血症 (FH)。更常见的 CAD 遗传风险是多个较高频率变体的函数，每个变体都赋予较低程度的风险，这些变体可以组合形成多基因风险评分 (PRS)，在极端情况下向个体传达重大风险。然而，PRS 的临床验证仍然存在差距，尤其是在非欧洲人群中。

概括

随着基因组测序技术的改进和更广泛地应用，冠状动脉疾病的遗传基础正在被揭开。因此，多基因风险评估有望成为临床环境中广泛使用且强大的工具。虽然使用 PRS 来增加当前的临床风险分层，以通过改变生活方式或靶向治疗来优化心血管疾病风险是有希望的，但我们等待充分有力的前瞻性研究，证明多基因风险估计在实践中的临床效用。