Functional Genomics: A Phenome-wide Survey

基因组学领域的两个主要发展为本提案的目标提供了信息。 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， 展示了一种具有成本效益和快速的人类基因发现方法， 巨大的潜力，揭示性状相关的基因座迄今为止无法实现，因为不充分的 权力或难以获得的表型。与此同时，功能基因组学正在产生大量的 基因组中的功能元件目录，使用广泛的分子测定， 不同的组织、细胞类型或状况。该提案将制定一种综合方法 这推进了我们对遗传学的生理机制的理解， 变异影响疾病风险或数量性状。基于现有研究 合作，这项工作将开发一套分析方法和计算工具， 分析人类医学表型，并提出了一个新的框架， 基因功能，使用与广泛的EHR数据相关联的大规模生物库（BioVU，UKBiobank， 和我们所有人）和功能基因组学数据的巨大广度（来自GTEx和其他 正在生产的企业。我们将开发一项新的全表型关联研究 （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.