Genetic and Environmental Risk Factors for Hemorrhagic Stroke

描述（由申请人提供）：颅内出血（ICH）是卒中致残率和死亡率最高的亚型。一半的死亡发生在中风后的头2天；把预防放在首位。这种竞争性更新建立在过去八年中出血性卒中病例和基于人群的控制的收集基础上。尽管有证据表明脑出血有遗传成分，但尚未对常见形式的脑出血进行全基因组连锁研究。这可能是因为发病晚和死亡率高，使得难以确定在世的受影响亲属对。我们的长期目标是确定新的危险因素和预防脑出血的治疗方法。因此，我们建议使用Affymetrix 6.0芯片对1072例ICH病例进行全基因组关联研究，并与2144例基于人群的、人口统计学匹配的对照组进行比较。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进行的血液样本和招募率数据。我们的主要假设是，特定的snp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，能够高效、经济地开展全基因组关联研究，对照研究是从人群中随机选择的，从与病例相同的人群中抽取，并且由于该研究基于人群的性质，可以估计风险因素对脑出血总体发病率的重要性。我们中心拥有完善的表型分析方法，并在研究设计、方法和分析的每个阶段都有专家参与。公共卫生相关性：脑出血是一种脑内血管破裂的中风。在中风的亚型中，它的死亡率和致残率最高，虽然治疗方法正在开发中，但最好的防御措施是防止脑出血。我们的研究共检查了1072例病例和2144例对照病例，并观察了906000个基因突变，以确定是否有任何基因突变与脑出血有关。从短期来看，我们的研究结果可能会导致确定脑出血风险最高的测试，从长期来看，可能会导致确定治疗和预防这种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.