sites - The NINDS International Stroke Genetics Consortium Study

项目总结（见说明）： 本申请的长期目标是表征中风易感性的遗传基础，以开发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，为未来这种疾病的遗传研究奠定基础。该提案建立在国际卒中遗传学协会（International Stroke Genetics） 联合会（ISGC）。对于目前的建议，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、缺血性中风研究、缺血性中风遗传学研究、大辛辛那提/北方肯塔基州中风研究、北方曼哈顿 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.收集缺血性卒中表型数据和来自10项卒中研究的高质量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例研究特定对照。表型数据将得到统一，新的全基因组基因分型将在估计的4，420例病例中进行， 3，277个控制器。 2.在这个10项研究的联盟中，根据亚型严格分类，测试与缺血性卒中的相关性。将进行研究特定分析，并将这些结果合并用于缺血性卒中及其亚型的荟萃分析，次要分析涉及亚群，包括人种/种族、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Wellcome Trust病例对照联合会、澳大利亚国家研究理事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。

PROJECT SUMMARY (See instructions): 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.