Stanford Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Department off Medicine, Stanford University School of Medicine, Stanford, CA.
Circ Genom Precis Med. 2021 Feb;14(1):e002964. doi: 10.1161/CIRCGEN.120.002964. Epub 2021 Feb 1.
The rich tradition of cardiovascular genomics has placed the field in prime position to extend our knowledge toward a genome-first approach to diagnosis and therapy. Population-scale genomic data has enabled exponential improvements in our ability to adjudicate variant pathogenicity based on allele rarity, and there has been a significant effort to employ these sizeable data in the investigation of rare disease. Certainly, population genomics data has great potential to aid the development of a genome-first approach to Mendelian cardiovascular disease, but its use in the clinical and investigative decision making is limited by the characteristics of the populations studied, and the evolutionary constraints on human Mendelian variation. To truly empower clinicians and patients, the successful implementation of a genome-first approach to rare cardiovascular disease will require the nuanced incorporation of population-based discovery with detailed investigation of rare disease cohorts and prospective variant evaluation.
心血管基因组学的丰富传统使该领域处于有利地位，能够将我们的知识扩展到以基因组为基础的诊断和治疗方法。基于等位基因稀有性，基于人群的基因组数据已经使我们裁决变异致病性的能力得到了指数级的提高，并且已经做出了巨大的努力来利用这些大量的数据来研究罕见疾病。当然，人群基因组学数据在辅助孟德尔心血管疾病的以基因组为基础的方法的发展方面具有巨大的潜力，但是由于研究人群的特征以及人类孟德尔变异的进化限制，其在临床和研究决策中的应用受到限制。为了真正赋予临床医生和患者权力，成功实施以基因组为基础的罕见心血管疾病方法将需要将基于人群的发现与对罕见疾病队列的详细研究和前瞻性变异评估细致地结合起来。
