The NINDS International Stroke Genetics Consortium Study

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，以便制定更有效的预防和治疗策略。我们的研究将彻底验证常见变异在中风中起主要作用的假设，为未来对这种疾病的遗传研究奠定基础。这项建议建立在国际中风遗传学协会（ISGC）建立的创新合作网络的基础上。对于目前的建议，来自美国的ISGC成员组成了一个较小的财团，其中包括以下研究：巴尔的摩-华盛顿青年中风研究、缺血性中风的兄弟姐妹研究、缺血性中风遗传学研究、大辛辛那提/肯塔基州北部中风研究、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、中风的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。收集来自10项卒中研究的缺血性卒中表型数据和高质量DNA样本或基因型数据，这些研究涉及7,033例缺血性卒中病例和23,411例研究特异性对照。表型数据将被统一，新的全基因组基因分型将对大约4,420例病例和3,277例对照进行。2. 在这个10项研究的联合研究中，对缺血性中风的相关性进行测试，严格按照亚型分类。将进行特定研究分析，并将这些结果结合起来进行缺血性卒中及其亚型的荟萃分析，并对亚人群进行二次分析，包括种族/民族、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，包括威康信托病例对照联盟、澳大利亚国家研究委员会研究和基因组流行病学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。

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.