GWAS of Venous Thrombosis

静脉血栓形成的 GWAS

• 批准号: 7514773
• 负责人: John A. Heit
• 金额: $ 56.66万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-20 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7514773
• 关键词: Acute; African American; Age; Anticoagulants; Arts; Candidate Disease Gene; Catheters; Centers for Disease Control and Prevention (U.S.); Clinic; Clinical; Cohort Studies; Complex; County; DNA; Data; Databases; Diagnosis; Disease; Disease susceptibility; Environment; Environmental Exposure; Environmental Risk Factor; Etiology; Event; Factor V Leiden mutation; Family; Frequencies; Funding; Gender; Genes; Genetic; Genetic Predisposition to Disease; Genotype; Goals; Hemostatic function; Heritability; Image; Incidence; Individual; Inflammation; Investigation; Link; Malignant Neoplasms; Methods; Mutation; Myocardial Infarction; Natural Immunity; Numbers; Office for Human Research Protections; Parents; Pathway Analysis; Pathway interactions; Patients; Physicians; Population; Predisposition; Prevention Research; Prophylactic treatment; Recruitment Activity; Recurrence; Reporting; Research; Research Design; Research Personnel; Risk; Risk Factors; SAS; Sample Size; Sampling; Siblings; Single Nucleotide Polymorphism; Single Nucleotide Polymorphism in Coding Sequence; Specific qualifier value; Stroke; Sudden Death; Susceptibility Gene; Testing; Thromboembolism; Thrombosis; Upper arm; Venous; Venous Thrombosis; Work; base; case control; cohort; experience; gene environment interaction; gene interaction; genetic variant; genome wide association study; improved; instrument; novel; prevent; proband; programs; residence; sex

DESCRIPTION (provided by applicant): Our overall long-term goal is to determine the etiology of the common and complex (multifactorial) disease, venous thromboembolism (VTE), by focusing on genetic and environmental factors that increase the risk of VTE, and the interactions among these factors. VTE is a common disease with over 900,000 incident or recurrent events in the U.S. annually; of these, almost one-third are fatal. To improve survival and avoid complications, VTE must be prevented. However, previous efforts to prevent VTE have been stymied because most individuals with known environmental (clinical) risk factors for VTE do not develop VTE. We hypothesize that, among those exposed to a clinical risk factor(s), a genetic predisposition distinguishes those who do from those who do not develop VTE. In support of this hypothesis, we have shown that VTE segregates in families due to heritability. VTE follows a complex mode of inheritance involving polygenes and environmental exposure. Our specific aims are: (1) to perform a genome wide association (GWA) screen and analysis using the 1M SNP platform specified by NHGRI genotyping facilities; (2) to test a)whether environmental exposures modify the observed relationship between genotype and VTE (geneenvironment interaction); and b) whether gene-gene interactions influence susceptibility to VTE; and 3) to test whether SNPs associated with VTE are located within or adjacent to genes that are functionally linked using pathway analysis. We currently have stored DNA samples from 829 VTE cases and 478 controls that are available for sharing with NHGRI, and by July 1, 2008, we project that we will have DNA samples from 1300 cases and 1300 controls. For all cases and controls, data on environmental exposures that are independent risk factors for VTE were collected with a standardized instrument. These data are stored in a SAS database by unique patient study number identifier and can be easily and rapidly shared. Using state of the art statistical genetic methods, we will identify genetic variants associated with VTE, including interactions. We will make the resulting data rapidly and widely available for research use and work collaboratively to share experience and expertise across participating biorepositories. Our results will have potentially great clinical utility by allowing physicians to stratify patients exposed to clinical risk factors into high- and low-VTE risk, identify unexposed patients at risk, and better target prophylaxis.

描述（由申请人提供）：我们的总体长期目标是确定常见和复杂（多因素）疾病，静脉血栓栓塞（VTE）的病因，通过关注增加VTE风险的遗传和环境因素，以及这些因素之间的相互作用。 VTE是一种常见疾病，每年在美国发生900,000多次事件或经常发生的事件；其中，几乎三分之一是致命的。为了提高生存并避免并发症，必须防止VTE。但是，以前为防止VTE的努力受到阻碍，因为大多数具有VTE的已知环境（临床）风险因素的人都不会发展VTE。我们假设，在暴露于临床危险因素的人中，遗传易感性将那些做的人与不发展VTE的人区分开。为了支持这一假设，我们表明VTE由于遗传力而在家庭中分离。 VTE遵循一种复杂的继承方式，涉及多基因和环境暴露。我们的具体目的是：（1）使用NHGRI基因分型设施指定的1M SNP平台执行基因组广泛的关联（GWA）屏幕； （2）测试a）环境暴露是否会改变观察到的基因型与VTE之间的关系（Geneenvormentment相互作用）； b）基因 - 基因相互作用是否影响对VTE的敏感性； 3）测试与VTE相关的SNP是否位于使用途径分析在功能上链接的基因内部或附近。目前，我们已经存储了来自829例VTE病例的DNA样品和478个对照，可与NHGRI共享，并在2008年7月1日之前预测，我们将提供来自1300例病例和1300个对照的DNA样品。对于所有情况和控制，使用标准化工具收集了有关VTE独立风险因素的环境暴露的数据。这些数据由独特的患者研究编号标识符存储在SAS数据库中，并且可以轻松，快速共享。使用最先进的统计遗传学方法，我们将确定与VTE相关的遗传变异，包括相互作用。我们将迅速和广泛地提供所得数据，以供研究和合作，以共享参与生物介绍的经验和专业知识。我们的结果将使医生能够将暴露于临床风险因素的患者分类为高VTE风险，识别有危险的未暴露患者并更好地靶向预防，从而具有出色的临床实用性。