Functional Genomics: A Phenome-wide Survey

功能基因组学：全表型组调查

• 批准号: 10652447
• 负责人: Eric R Gamazon
• 金额: $ 44.08万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10652447
• 关键词: Biological; Biological Assay; Catalogs; Collaborations; Computerized Medical Record; DNA; Data; Development; Electronic Health Record; Elements; Genetic; Genetic Variation; Genome; Genomics; Genotype-Tissue Expression Project; Growth; Human; Human Genetics; Human Genome; Link; Medical; Methodological Studies; Methodology; Molecular; Phenotype; Physiological; Process; Research; Statistical Methods; Surveys; Tissues; Work; biobank; cell type; computerized tools; cost effective; disorder risk; functional genomics; gene function; genetic analysis; genome wide association study; genomic data; genomic epidemiology; high throughput technology; human disease; novel; phenome; trait

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.

基因组学领域的两个主要发展介绍了该提案的目的。 最近使用与电子健康记录（EHR）相关的DNA生物库的大规模努力已有 证明了一种具有成本效益和快速的人类遗传发现的方法 发现与特征相关的基因座的巨大潜力迄今无法访问，因为不足 功率或难以进行的表型。同时，功能基因组学正在产生大型 基因组中功能元素的目录使用广泛的分子测定 多种组织，细胞类型或条件。该建议将开发一种综合方法 这可以提高我们对遗传学机制的理解 变异影响疾病风险或定量性状。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 对人类医学现象的分析，并为研究提供了一个新的框架 基因功能，使用与广泛EHR数据相关的大规模生物库（Biovu，UK Biobank， 以及我们所有人）以及功能基因组学数据的广度（来自GTEX和其他 正在生产的财团。我们将开发一项新的现象整个关联研究 （Phewas）方法论，一种发现和复制的方法，具有增强的功能 提出相关机制。

项目成果

Post-GWAS analysis of six substance use traits improves the identification and functional interpretation of genetic risk loci.

• DOI: 10.1016/j.drugalcdep.2019.107703
• 发表时间: 2020-01-01
• 期刊: DRUG AND ALCOHOL DEPENDENCE
• 影响因子: 4.2
• 作者: Marees, Andries T.;Gamazon, Eric R.;Gerring, Zachary;Vorspan, Florence;Fingal, Josh;van den Brink, Wim;Smit, Dirk J. A.;Verweij, Karin J. H.;Kranzler, Henry R.;Sherva, Richard;Farrer, Lindsay;Stringer, Sven;Minica, Camelia C.;Mbarek, Hamdi;Bernard, Manon;Derringer, Jaime;van Eijk, Kristel R.;Isen, Joshua D.;Loukola, Anu;Maciejewski, Dominique F.;Mihailov, Evelin;van der Most, Peter J.;Sanchez-Mora, Cristina;Roos, Leonie;Walters, Raymond;Ware, Jennifer J.;Abdellaoui, Abdel;Bigdeli, Timothy B.;Branje, Susan J. T.;Brown, Sandra A.;Bruinenberg, Marcel;Casas, Miguel;Esko, Tonu;Garcia-Martinez, Iris;Gordon, Scott D.;Harris, Juliette M.;Hartman, Catharina A.;Henders, Anjali K.;Heath, Andrew C.;Hickie, Ian B.;Hickman, Matthew;Hopfer, Christian J.;Hottenga, Jouke Jan;Huizink, Anja C.;Irons, Daniel E.;Kahn, Rene S.;Korhonen, Tellervo;Krauter, Ken;van Lier, Pol A. C.;Lubke, Gitta H.;Madden, Pamela A. F.;Magi, Reedik;McGue, Matt K.;Medland, Sarah E.;Meeus, Wim H. J.;Miller, Michael B.;Montgomery, Grant W.;Nivard, Michel G.;Nolte, Ilja M.;Oldehinkel, Albertine J.;Pausova, Zdenka;Qaiser, Beenish;Quaye, Lydia;Ramos-Quiroga, Josep A.;Richarte, Vanesa;Rose, Richard J.;Shin, Jean;Stallings, Michael C.;Stiby, Alex I.;Wall, Tamara L.;Wright, Margaret J.;Koot, Hans M.;Paus, Tomas;Hewitt, John K.;Ribases, Marta;Kaprio, Jaakko;Boks, Marco P.;Snieder, Harold;Spector, Tim;Munafo, Marcus R.;Metspalu, Andres;Boomsma, Dorret I.;Iacono, William G.;Martini, Nicholas G.;Gillespie, Nathan A.;Vink, Jacqueline M.;Gelernter, Joel;Derks, Eske M.
• 通讯作者: Derks, Eske M.