Promise and Peril of Population Genomics for the Development of Genome-First Approaches in Mendelian Cardiovascular Disease.
Promise and Peril of Population Genomics for the Development of Genome-First Approaches in Mendelian Cardiovascular Disease.
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种群基因组学对孟德尔心血管疾病基因组优先方法发展的希望和危险。
DOI：
10.1161/circgen.120.002964
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发表时间：
2021-03
期刊：
影响因子：
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通讯作者：
Parikh VN
中科院分区：
文献类型：
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作者：
Parikh VN
心血管基因组学的丰富传统使该领域处于领先地位，可以将我们的知识扩展到基因组优先的诊断和治疗方法。群体规模的基因组数据使我们根据等位基因稀有性判断变异致病性的能力呈指数级提高，并且我们在罕见疾病的研究中利用这些大量数据做出了巨大的努力。当然，群体基因组学数据具有帮助开发孟德尔心血管疾病基因组优先方法的巨大潜力，但其在临床和研究决策中的使用受到所研究群体的特征以及人类孟德尔变异的进化限制的限制。为了真正赋予临床医生和患者权力，成功实施罕见心血管疾病的基因组优先方法需要将基于人群的发现与罕见疾病队列的详细调查和前瞻性变异评估细致入微地结合起来。
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 are 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.