The NINDS International Stroke Genetics Consortium Study

NINDS 国际中风遗传学联盟研究

• 批准号: 7848501
• 负责人: George Howard
• 金额: $ 369.06万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7848501
• 关键词: NINDS; International; Stroke; Genetics; Consortium

DESCRIPTION (provided by applicant): The long-term objective of this application is to characterize the genetic basis for stroke susceptibility in order to develop more effective prevention and treatment strategies. Our study will thoroughly test the hypothesis that common variants play a major role in stroke, setting the stage for the future genetic study of this disease. This proposal builds on the innovative collaborative network established by the International Stroke Genetics Consortium (ISGC). For the present proposal, ISGC members from the USA have formed a smaller consortium, which includes the following studies: Baltimore-Washington Young Stroke Study, Siblings with Ischemic Stroke Study, Ischemic Stroke Genetics Study, Greater Cincinnati/Northern Kentucky Stroke Study, Northern Manhattan Study, Genes Affecting Stroke Risk and Outcome Study/Bugher Network Study, Heart and Vascular Health Stroke Study, Reasons for Geographic and Racial Differences in Stroke, Nurses Health Study, and Women's Health Initiative. Our specific aims are to: 1. Assemble ischemic stroke phenotypic data and either high quality DNA samples or genotype data from 10 stroke studies with access to 7,033 cases of ischemic stroke and 23,411 study-specific controls. Phenotype data will be harmonized and new genome-wide genotyping will be performed on an estimated 4,420 cases and 3,277 controls. 2. Test for associations with ischemic stroke, rigorously categorized according to subtypes, within this 10- study consortium. Study-specific analyses will be performed and these results will be combined for a metaanalysis of ischemic stroke and its subtypes, with secondary analyses addressing subpopulations, including race/ethnicity, gender, and age of onset. 3. Replicate and extend associations detected in Aim 2 above by taking advantage of other genome-wide association studies conducted by members of the ISGC, including the Wellcome Trust Case-Control Consortium, the Australian National Research Council Study, and the Cohorts for Heart and Aging Research in Genomic Epidemiology. PUBLIC HEALTH RELEVANCE: Stroke, defined as acute vascular disease of the brain, is the third leading cause of death and the leading cause of major disability. The long-range goal of our research is to characterize the genetic basis for stroke susceptibility in order to develop the effective prevention and treatment strategies that are desperately needed.

描述（由申请人提供）：本申请的长期目标是表征中风易感性的遗传基础，以制定更有效的预防和治疗策略。我们的研究将彻底检验常见变异在中风中发挥重要作用的假设，为未来对该疾病的遗传学研究奠定基础。该提案建立在国际中风遗传学联盟 (ISGC) 建立的创新合作网络的基础上。对于目前的提案，来自美国的 ISGC 成员组成了一个较小的联盟，其中包括以下研究：巴尔的摩-华盛顿年轻中风研究、缺血性中风兄弟姐妹研究、缺血性中风遗传学研究、大辛辛那提/北肯塔基州中风研究、曼哈顿北部研究、影响中风风险和结果的基因研究/Bugher 网络研究、心脏和血管健康中风研究、地理和种族原因中风、护士健康研究和妇女健康倡议的差异。我们的具体目标是： 1. 收集来自 10 项中风研究的缺血性中风表型数据和高质量 DNA 样本或基因型数据，涉及 7,033 例缺血性中风病例和 23,411 个研究特定对照。表型数据将得到统一，并对估计 4,420 例病例和 3,277 例对照进行新的全基因组基因分型。 2. 在这 10 项研究联合体中，测试与缺血性中风的关联，并根据亚型严格分类。将进行特定于研究的分析，并将这些结果结合起来对缺血性中风及其亚型进行荟萃分析，并针对亚群进行二次分析，包括种族/族裔、性别和发病年龄。 3. 利用 ISGC 成员进行的其他全基因组关联研究（包括 Wellcome Trust 病例对照联盟、澳大利亚国家研究委员会研究以及心脏和心脏队列研究）来复制和扩展上述目标 2 中检测到的关联。基因组流行病学的衰老研究。 公众健康相关性：中风被定义为脑部急性血管疾病，是第三大死因，也是导致重大残疾的主要原因。我们研究的长期目标是确定中风易感性的遗传基础，以便制定迫切需要的有效预防和治疗策略。