From the Cardiovascular Research Center, Massachusetts General Hospital, Boston; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA; and Department of Medicine, Harvard Medical School, Boston, MA.
Circ Res. 2020 Apr 24;126(9):1159-1177. doi: 10.1161/CIRCRESAHA.120.315928. Epub 2020 Apr 23.
An individual's susceptibility to atherosclerotic cardiovascular disease is influenced by numerous clinical and lifestyle factors, motivating the multifaceted approaches currently endorsed for primary and secondary cardiovascular disease prevention. With growing knowledge of the genetic basis of atherosclerotic cardiovascular disease-in particular, coronary artery disease-and its contribution to disease pathogenesis, there is increased interest in understanding the potential clinical utility of a genetic predictor that might further refine the assessment and management of atherosclerotic cardiovascular disease risk. Rapid scientific and technological advances have enabled widespread genotyping efforts and dynamic research in the field of coronary artery disease genetic risk prediction. In this review, we describe how genomic analyses of coronary artery disease have been leveraged to create polygenic risk scores. We then discuss evaluations of the clinical utility of these scores, pertinent mechanistic insights gleaned, and practical considerations relevant to the implementation of polygenic risk scores in the health care setting.
个体易患动脉粥样硬化性心血管疾病受到许多临床和生活方式因素的影响，这促使人们目前采用多方面的方法来进行一级和二级心血管疾病的预防。随着对动脉粥样硬化性心血管疾病（尤其是冠状动脉疾病）遗传基础及其在疾病发病机制中的作用的了解不断增加，人们越来越关注理解遗传预测因子的潜在临床应用价值，这可能进一步完善动脉粥样硬化性心血管疾病风险的评估和管理。快速的科学技术进步使得广泛的基因分型工作和冠状动脉疾病遗传风险预测领域的动态研究成为可能。在这篇综述中，我们描述了如何利用冠状动脉疾病的基因组分析来创建多基因风险评分。然后，我们讨论了这些评分的临床实用性评估、从中获得的相关机制见解，以及与在医疗保健环境中实施多基因风险评分相关的实际考虑因素。
