Next steps in cardiovascular disease genomic research--sequencing, epigenetics, and transcriptomics.
Next steps in cardiovascular disease genomic research--sequencing, epigenetics, and transcriptomics.
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DOI：
10.1373/clinchem.2011.170423
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发表时间：
2012-01
影响因子：
9.3
通讯作者：
Benjamin EJ
中科院分区：
文献类型：
--
作者：
Schnabel RB;Baccarelli A;Lin H;Ellinor PT;Benjamin EJ
心血管疾病（CVD）的基因组研究在过去五年中进展迅速。然而，在大多数情况下，这些突破性的观察结果还没有伴随着临床适用的风险预测，诊断或治疗干预工具。我们回顾了英文文献中的新方法和有前途的基因组靶点，这将允许大规模筛选和随访最近的CVD基因组发现。我们预计，三个关键领域的进展将是这些项目成功的关键。首先，以外显子组为中心的下一代全基因组测序将识别与心血管疾病及其危险因素相关的罕见和新型遗传变异。方法的改进也将大大推进人类表观遗传学和基因表达领域。其次，研究越来越多地承认，静态DNA序列变异只能解释一小部分遗传表型。因此，我们预期多重表观遗传和基因表达特征将在实验和临床环境中与CVD相关。利用现有的大规模联盟和临床生物库与电子健康记录相结合，有望整合流行病学和临床基因组学数据。最后，需要一种系统生物学方法来整合积累的多维数据。测序、表观遗传学和转录组学的新方法以及前所未有的大规模合作努力有望深入了解复杂的CVD。知识的快速积累和整合将揭示相当大比例的CVD遗传力缺失。
Genomic research in cardiovascular disease (CVD) has progressed rapidly over the last five years. However, in most cases these ground-breaking observations have not yet been accompanied by clinically applicable tools for risk prediction, diagnosis, or therapeutic interventions. We reviewed the English literature for novel methods and promising genomic targets that will permit large-scale screening and follow-up of recent genomic findings for CVD. We anticipate that advances in three key areas will be critical for the success of these projects. First, exome-centered and whole genome next generation sequencing will identify rare and novel genetic variants associated with CVD and its risk factors. Improvements in methods will also greatly advance the field of epigenetics and gene expression in humans. Second, research increasingly acknowledges that static DNA sequence variation explains only a fraction of the inherited phenotype. Therefore we expect that multifold epigenetic and gene expression signatures will be related to CVD in experimental and clinical settings. Leveraging existing large-scale consortia and clinical biobanks combined with electronic health records holds promise to integrate epidemiological and clinical genomics data. Finally, a systems biology approach will be needed to integrate the accumulated multidimensional data. Novel methods in sequencing, epigenetics and transcriptomics, and unprecedented large-scale cooperative efforts promise to generate insights into complex CVD. The rapid accumulation and integration of knowledge will shed light onto the considerable proportion of the missing heritability of CVD.