Functional Genomics: A Phenome-wide Survey

基因组学领域的两个主要发展为这项提议的目标提供了信息。 最近使用与电子健康记录(EHR)相关联的DNA生物库的大规模努力已经 展示了一种具有成本效益和快速的人类基因发现方法 发现性状相关基因的巨大潜力到目前为止由于不充分的 权势或难以获得的表型。与此同时，功能基因组学正在产生大量 使用广谱分子分析的基因组功能元件目录 不同的组织、细胞类型或条件。这项提议将形成一种综合方法论 这促进了我们对基因通过 变异会影响疾病风险或数量性状。建立在现有研究的基础上 协作，这项工作将开发一套分析方法和计算工具 对人类医学现象的分析为研究人类医学现象提供了一个新的框架 基因功能，使用链接到广泛的EHR数据的大规模生物库(BioVU，UK Biobank， 和我们所有人)和大量的功能基因组数据(来自GTEx和其他 财团)，正在生产。我们将开发一项新的全物候组关联研究 (Phewas)方法，一种具有增强功能的发现和复制方法 提出相关机制。

Two major developments in the field of Genomics inform the aims of this proposal. Recent large-scale efforts using DNA biobanks linked to electronic health records (EHR) have demonstrated a cost-effective and rapid approach to human genetic discovery with the enormous potential to uncover trait-associated loci hitherto inaccessible because of inadequate power or difficult-to-procure phenotypes. Meanwhile, Functional Genomics is generating large catalogs of functional elements in the genome using a broad spectrum of molecular assays in diverse tissues, cell types, or conditions. This proposal will develop an integrative methodology that advances our understanding of the physiological mechanisms through which genetic variation influences disease risk or quantitative trait. Building on existing research collaborations, this work will develop a set of analytic approaches and computational tools for the analysis of the human medical phenome and present a novel framework for the study of gene function, using large-scale biobanks linked to extensive EHR data (BioVU, UK Biobank, and All of Us) and the enormous breadth of functional genomics data (from GTEx and other consortia) that are being produced. We will develop a new Phenome-Wide Association Study (PheWAS) methodology, an approach to discovery and replication with enhanced capabilities for proposing relevant mechanisms.