Platform for Accelerating Genetic Discovery for Cerebrovascular Disease

加速脑血管疾病基因发现的平台

• 批准号: 9303463
• 负责人: JONATHAN ROSAND
• 金额: $ 28.86万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9303463
• 关键词: Adult; Biological Process; Biology; Cause of Death; Cerebrovascular Disorders; Classification; Clinical Data; Collaborations; Collection; Communities; Computer software; Computerized Medical Record; Custom; DNA; Data; Data Analyses; Data Discovery; Data Set; Development; Diagnosis; Enrollment; Ensure; Ethics Committees; Evaluation; Funding; Future; Genetic; Genetic study; Genome; Genotype; Goals; Growth; Hospital Records; Human; Human Genetics; Image; Individual; Informed Consent; Institutional Review Boards; International; Investments; Location; Magnetic Resonance Imaging; Maintenance; Medical; Meta-Analysis; Mission; National Institute of Neurological Disorders and Stroke; Patients; Phenotype; Prevention; Principal Investigator; Process; Protocols documentation; Quality Control; Research; Research Infrastructure; Research Personnel; Resources; Risk; Sampling; Stroke; Stroke prevention; Structure; Technology; Testing; Time; Variant; computing resources; cost; data access; data integration; data sharing; disability; disorder risk; effective therapy; falls; flexibility; genetic resource; genetic variant; genome-wide; genome-wide analysis; human subject protection; improved; innovation; neuroimaging; new therapeutic target; novel; operation; petabyte; phenotypic data; programs; public health relevance; research clinical testing; research study; routine care; statistics; stroke treatment; tool

 DESCRIPTION (provided by applicant): Despite substantial advances in its treatment and prevention, stroke remains the second-leading cause of death worldwide and the leading cause of major disability among adults. Identifying the biological processes that underlie the cerebrovascular diseases that cause stroke is crucial to guiding the development of safe and effective therapies. The dramatic fall in cost of genome-wide genotyping and sequencing has made it possible to systematically collect vast amounts of data on individual genome variation. In parallel with advances in genotyping and sequencing technology, there has been a substantial increase in the availability and complexity of data characterizing patients. Neuroimaging, via CT and often MRI, is very frequently obtained during routine clinical evaluation and classification of stroke subtype can now be comprehensively ascertained using online tools that require and retain large amounts of primary data from medical evaluations. Finally, electronic medical records now retain increasing amounts of data on patients enrolled in research studies. By generating and analyzing genome-wide genotypes and collecting and analyzing extensive imaging and phenotype data in thousands of individuals with stroke, the International Stroke Genetics Consortium (ISGC) has made substantial progress in identifying the genetic variants that influence risk of stroke, the initial step in the discovery cycle. Nonetheless, substantial barriers remain to leveraging these and future data for the advancement of our understanding of cerebrovascular disease and the ultimate development of novel therapeutic targets for stroke. Datasets are (1) of unprecedented scale, (2) disparate in location, and (3) heterogeneous in type. As a result, the research community lacks the data access and integration necessary in order to perform valid and well-powered comparisons to generate new hypotheses and improve our understanding of cerebrovascular disease biology. We propose to create new infrastructure for the wide sharing of human genetic, phenotypic and neuroimaging data for the purpose of accelerating the search for effective treatments for cerebrovascular disease. The Platform for accelerating genetic discovery for cerebrovascular disease will overcome these three barriers by creating a flexible and scalable resource for the investigative community that integrates genetic datasets containing individual-level genotyping results, incorporating over 30,000 stroke cases and appropriate stroke- free controls collected from dozens of centers around the world, all having undergone centralized quality control according to a single streamlined approach, and all made available through an ethics committee- approved process for rapid sharing with any investigator world-wide. Governed by a steering committee made up of long-standing collaborators in stroke genetics, this resource will transform the genetic study of stroke in humans, providing a durable resource that can ultimately be sustained by the established collaborative culture of the ISGC and small subsidies from researchers who utilize the Platform

 描述（由适用提供）：尽管在治疗和预防方面取得了长足的进步，但中风仍然是全球死亡的第二大原因，也是成年人重大残疾的主要原因。确定引起中风的脑血管疾病基础的生物学过程对于指导安全有效疗法的发展至关重要。全基因组基因分型和测序的成本急剧下降使系统地收集有关单个基因组变异的大量数据成为可能。与基因分型和测序技术的进步同时，表征患者的数据的可用性和复杂性已大大提高。通过CT和经常MRI，神经影像学经常在常规临床评估和中风子类型的分类过程中经常获得，现在可以使用在线工具中全面确定并从医学评估中保留大量主要数据。最后，电子病历现在保留了越来越多的研究研究患者的数据。通过生成和分析全基因组基因型，并在数千个患有中风的个体中收集和分析广泛的成像和表型数据，国际卒中遗传学联盟（ISGC）在识别影响中风风险的遗传变异方面取得了重大进展，这是发现周期的初始步骤。尽管如此，仍有实质性的障碍仍在利用这些和未来的数据，以促进我们对脑血管疾病的理解以及中风的新型治疗靶标的最终发展。数据集是（1）的前所未有的比例，（2）位置不同，（3）类型异质。结果，研究界缺乏必要的数据访问和集成，以便进行有效且能力充分的比较来产生新的假设并提高我们对脑血管疾病生物学的理解。我们建议为人类遗传，表型和神经成像数据的广泛共享创建新的基础设施，以加速寻找有效治疗脑血管疾病的治疗方法。加速脑血管疾病遗传发现的平台将通过为调查社区创建灵活且可伸缩的资源来克服这三个障碍批准与全球任何调查员快速共享的过程。该资源由由中风遗传学的长期合作者组成的指导委员会支配，该资源将改变人类中风的遗传研究，提供持久的资源，最终可以由ISGC的既定协作文化以及利用该平台的研究人员提供的小型补贴来维持。