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（由申请人提供）：尽管在治疗和预防方面取得了实质性进展，但中风仍然是全球第二大死亡原因，也是成人主要残疾的主要原因。识别导致中风的脑血管疾病的生物学过程对于指导安全有效疗法的开发至关重要。全基因组基因分型和测序成本的大幅下降使得系统地收集关于个体基因组变异的大量数据成为可能。在基因分型和测序技术进步的同时，表征患者的数据的可用性和复杂性也大幅增加。在常规临床评估期间，通过CT和通常MRI进行的神经成像非常频繁，并且现在可以使用在线工具全面确定中风亚型的分类，这些工具需要并保留来自医学评估的大量原始数据。最后，电子医疗记录现在保留了越来越多的参与研究的患者数据。通过生成和分析全基因组基因型，并收集和分析数千名中风患者的广泛成像和表型数据，国际中风遗传学联盟（ISGC）在识别影响中风风险的遗传变异方面取得了实质性进展，这是发现周期的第一步。尽管如此，利用这些和未来的数据来促进我们对脑血管疾病的理解和最终开发中风的新治疗靶点仍然存在重大障碍。数据集（1）规模空前，（2）位置不同，（3）类型异构。因此，研究界缺乏必要的数据访问和整合，以进行有效和有力的比较，以产生新的假设，并提高我们对脑血管疾病生物学的理解。我们建议建立新的基础设施，广泛共享人类遗传、表型和神经影像学数据，以加速寻找脑血管疾病的有效治疗方法。加速脑血管疾病遗传发现的平台将通过为研究社区创建灵活和可扩展的资源来克服这三个障碍，该资源整合了包含个体水平基因分型结果的遗传数据集，整合了从世界各地数十个中心收集的30，000多例卒中病例和适当的无卒中对照，所有这些都根据单一的简化方法进行了集中质量控制，所有这些都通过伦理委员会批准的程序提供，以便与世界各地的任何研究者快速共享。由中风遗传学长期合作者组成的指导委员会管理，该资源将改变人类中风的遗传学研究，提供持久的资源，最终可以通过ISGC的既定合作文化和使用该平台的研究人员的小额补贴来维持。