J Clin Invest. 2020 Jan 2;130(1):29-38. doi: 10.1172/JCI129203.
Advanced phenotyping of cardiovascular diseases has evolved with the application of high-resolution omics screening to populations enrolled in large-scale observational and clinical trials. This strategy has revealed that considerable heterogeneity exists at the genotype, endophenotype, and clinical phenotype levels in cardiovascular diseases, a feature of the most common diseases that has not been elucidated by conventional reductionism. In this discussion, we address genomic context and (endo)phenotypic heterogeneity, and examine commonly encountered cardiovascular diseases to illustrate the genotypic underpinnings of (endo)phenotypic diversity. We highlight the existing challenges in cardiovascular disease genotyping and phenotyping that can be addressed by the integration of big data and interpreted using novel analytical methodologies (network analysis). Precision cardiovascular medicine will only be broadly applied to cardiovascular patients once this comprehensive data set is subjected to unique, integrative analytical strategies that accommodate molecular and clinical heterogeneity rather than ignore or reduce it.
心血管疾病的高级表型分析随着高通量组学筛选在大规模观察性和临床试验中被应用于人群而发展。这一策略揭示了心血管疾病在基因型、中间表型和临床表型水平上存在着相当大的异质性,这是最常见疾病的特征,传统的还原论方法并没有阐明这一点。在本次讨论中,我们将讨论基因组背景和(中间)表型异质性,并研究常见的心血管疾病,以阐明(中间)表型多样性的基因型基础。我们强调了心血管疾病基因分型和表型分析中存在的挑战,可以通过整合大数据并使用新的分析方法(网络分析)进行解释来解决。只有当这个综合数据集经过独特的、综合的分析策略处理后,这些策略可以适应分子和临床异质性,而不是忽略或简化它们,才能将精准心血管医学广泛应用于心血管患者。