Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (C. Li, R.Z., Z.H., X.S.).
Division of Nephrology, Department of Medicine, College of Medicine, University of Illinois Chicago (Y.P., D.L., Y.H., C.L., V.R., T.N.K.).
Circ Res. 2023 Jun 9;132(12):1628-1647. doi: 10.1161/CIRCRESAHA.123.321999. Epub 2023 Jun 8.
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. Although CVD events do not typically manifest until older adulthood, CVD develops gradually across the life-course, beginning with the elevation of risk factors observed as early as childhood or adolescence and the emergence of subclinical disease that can occur in young adulthood or midlife. Genomic background, which is determined at zygote formation, is among the earliest risk factors for CVD. With major advances in molecular technology, including the emergence of gene-editing techniques, along with deep whole-genome sequencing and high-throughput array-based genotyping, scientists now have the opportunity to not only discover genomic mechanisms underlying CVD but use this knowledge for the life-course prevention and treatment of these conditions. The current review focuses on innovations in the field of genomics and their applications to monogenic and polygenic CVD prevention and treatment. With respect to monogenic CVD, we discuss how the emergence of whole-genome sequencing technology has accelerated the discovery of disease-causing variants, allowing comprehensive screening and early, aggressive CVD mitigation strategies in patients and their families. We further describe advances in gene editing technology, which might soon make possible cures for CVD conditions once thought untreatable. In relation to polygenic CVD, we focus on recent innovations that leverage findings of genome-wide association studies to identify druggable gene targets and develop predictive genomic models of disease, which are already facilitating breakthroughs in the life-course treatment and prevention of CVD. Gaps in current research and future directions of genomics studies are also discussed. In aggregate, we hope to underline the value of leveraging genomics and broader multiomics information for characterizing CVD conditions, work which promises to expand precision approaches for the life-course prevention and treatment of CVD.
心血管疾病（CVD）是全球发病率和死亡率的主要原因。尽管 CVD 事件通常直到成年后才会出现，但 CVD 是在整个生命过程中逐渐发展的，从儿童或青少年时期观察到的风险因素升高开始，到可能在青年或中年出现的亚临床疾病开始。基因组背景是在合子形成时确定的，是 CVD 的最早风险因素之一。随着分子技术的重大进步，包括基因编辑技术的出现，以及全基因组测序和高通量基于阵列的基因分型的深入发展，科学家们现在不仅有机会发现 CVD 背后的基因组机制，还可以利用这些知识来预防和治疗这些疾病。本综述重点介绍了基因组学领域的创新及其在单基因和多基因 CVD 预防和治疗中的应用。关于单基因 CVD，我们讨论了全基因组测序技术的出现如何加速了致病变异的发现，使患者及其家属能够进行全面筛查和早期、积极的 CVD 缓解策略。我们进一步描述了基因编辑技术的进展，该技术可能很快就能为曾经认为无法治疗的 CVD 疾病提供治疗方法。关于多基因 CVD，我们专注于最近利用全基因组关联研究结果来确定可用药基因靶点和开发疾病预测性基因组模型的创新，这些创新已经在 CVD 的生命过程治疗和预防方面取得了突破。我们还讨论了当前研究中的差距和未来基因组学研究的方向。总的来说，我们希望强调利用基因组学和更广泛的多组学信息来描述 CVD 疾病的价值，这项工作有望扩大 CVD 生命过程预防和治疗的精准方法。
