Genetic and Environmental Risk Factors for Hemorrhagic Stroke

描述(申请人提供)：脑出血(ICH)是中风中致残率和死亡率最高的亚型。一半的死亡率发生在中风后的头两天；因此预防至关重要。这一竞争性更新建立在过去八年收集的出血性中风和以人口为基础的控制病例的基础上。尽管有证据表明脑出血存在遗传成分，但尚未对常见形式的脑出血进行全基因组范围的连锁研究。这很可能是因为发病晚，死亡率高，这使得识别在世的受影响亲属对变得困难。我们的长期目标是确定新的危险因素和治疗方法来预防脑出血。因此，我们建议使用Affymetrix 6.0芯片对1,072例脑出血患者和2,144例基于人群、人口统计学匹配的对照组进行全基因组相关性研究。我们的初步数据包括使用我们研究早期的口腔拭子进行的实际基因分型，以及使用所提出的方法的血液样本和招募比率的数据。我们的主要假设是，特定的SNPs将与脑出血相关，独立于传统的危险因素，包括高血压、糖尿病、吸烟、饮酒和载脂蛋白E等位基因。我们的中心具有独特的优势，可以有效和经济地进行全基因组相关性研究，对照是从人群中随机选择的，来自与病例相同的人群，由于研究的人群性质，提供了风险因素对脑出血总体发病率的重要性的估计。我们中心有一套完善的表型分析方法，并邀请专家参与研究设计、方法学和分析的每个阶段。公共卫生相关性：脑出血是一种脑血管破裂的中风类型。在中风的亚型中，它的死亡率和致残率最高，在开发治疗方法的同时，最好的防御措施是预防脑出血。我们的研究检查了来自与病例相同的人群的总共1,072例病例和2,144名对照，并观察了906,000个基因突变，以确定它们中是否有任何一个与脑内出血有关。在短期内，我们的发现可能会导致确定可以进行的测试，以确定脑内出血的最高风险者，并在长期内，确定治疗和预防这一致命亚型中风的新靶点。

DESCRIPTION (provided by applicant): Intracerebral hemorrhage (ICH) is the subtype of stroke with the highest disability and mortality rates. Half of the mortality occurs in the first 2 days after stroke; making prevention of paramount importance. This competitive renewal builds upon the collection of cases of hemorrhagic stroke and population-based controls over the past eight years. Despite evidence for a genetic component for ICH, no genome-wide linkage studies for common forms of ICH have been performed. This is likely because of the late onset and high mortality rate which makes identifying living affected relative pairs difficult. Our long- term goal is to identify new risk factors and treatments to prevent ICH. Thus, we propose to perform a genome-wide association study of 1,072 cases of ICH compared to 2,144 population-based, demographically matched controls using the Affymetrix 6.0 Chip. Our preliminary data includes actual genotyping using buccal swabs from the early part of our study as well as blood samples and data on the recruitment rate using the methods proposed. Our primary hypothesis is that specific SNPs will be associated with ICH independent of traditional risk factors including hypertension, diabetes, smoking, alcohol use and Apolipoprotein E alleles. Our center is uniquely positioned to efficiently and economically perform a genome-wide association study with controls that have been randomly selected from the population, drawn from the same population as cases and because of the population-based nature of the study, provide an estimate of how important a risk factor may be to the overall incidence of ICH. Our center has a well- established phenotyping methodology and brings experts to each stage of the study design, methodology and analysis. PUBLIC HEALTH RELEVANCE: Intracerebral hemorrhage is a type of stroke where blood vessels rupture in the brain. Of the subtypes of stroke, it has the highest rates of death and disability and while treatments are being developed, the best defense is to prevent intracerebral hemorrhage. Our study examines a total of 1,072 cases and 2,144 controls from the same population as the cases and looks at 906,000 genetic mutations to see if any of them are associated with intracerebral hemorrhage. In the short-term, our findings may lead to identification of tests that can be performed to identify those at highest risk for intracerebral hemorrhage and in the long-term, to the identification of novel targets for treatment and prevention of this deadly subtype of stroke.