The NINDS International Stroke Genetics Consortium Study

描述(由申请人提供)：本申请的长期目标是确定中风易感性的遗传基础，以便开发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主要作用的假设，为未来对这种疾病的遗传学研究奠定基础。这项建议建立在国际中风遗传学联合会(ISGC)建立的创新合作网络的基础上。在目前的提案中，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-华盛顿青年中风研究、兄弟姐妹缺血性中风研究、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/布格尔网络研究、心脏和血管健康中风研究、中风中地理和种族差异的原因、护士健康研究和妇女健康倡议。我们的具体目标是：1.收集缺血性中风表型数据和来自10个中风研究的高质量DNA样本或基因数据，获得7,033例缺血性中风病例和23,411个研究特定对照。表型数据将得到协调，估计将对4420例患者和3277名对照进行新的全基因组基因分型。2.在这个由10人组成的研究联盟中，根据亚型严格分类，测试与缺血性中风的相关性。将进行特定于研究的分析，这些结果将被结合起来，用于对缺血性中风及其亚型的荟萃分析，以及针对亚群的二次分析，包括种族/民族、性别和发病年龄。3.通过利用ISGC成员进行的其他全基因组关联研究，包括惠康信托病例对照联盟、澳大利亚国家研究委员会研究以及基因组流行病学中的心脏和衰老研究队列，复制和扩展上述目标2中检测到的关联。 公共卫生相关性：中风被定义为急性脑血管疾病，是导致死亡的第三大原因和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，以便开发迫切需要的有效预防和治疗策略。

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.