Genetic and Environmental Risk Factors for Hemorrhagic Stroke

摘要 脑出血（ICH）是脑卒中中致残率最高的亚型， 死亡率。一半的死亡发生在中风后的前2天; 预防至关重要。这一竞争性的更新建立在收集 出血性中风病例和基于人群的控制。 尽管有证据表明ICH的遗传成分，但没有全基因组连锁研究， 常见形式的ICH已被执行。这可能是因为晚发病， 死亡率高，难以确定受影响的亲属对。我们长久以来- 长期目标是确定新的危险因素和治疗方法以预防ICH。因此，我们建议 对1,072例ICH病例进行全基因组关联研究， 基于人群的、人口统计学匹配的对照，使用Affysse6.0芯片。我们 初步数据包括使用口腔拭子进行的实际基因分型， 我们的研究以及血液样本和数据的招募率使用的方法 提出了我们的主要假设是特定的SNPs与ICH相关 独立于传统的风险因素，包括高血压、糖尿病、吸烟、饮酒 使用和载脂蛋白E等位基因。我们的中心具有独特的优势， 经济地进行全基因组关联研究， 从人群中随机选择，从与病例相同的人群中抽取， 由于研究的人群基础性质，提供如何 一个重要的风险因素可能是ICH的总体发病率。我们的中心有一个很好的- 建立了表型分析方法，并将专家带到研究的每个阶段 设计、方法和分析。敷设总结 脑出血是一种脑血管破裂的中风。 在中风的亚型中，它的死亡率和残疾率最高， 治疗方法正在开发中，最好的防御措施是防止脑出血。 我们的研究共调查了来自同一人群的1,072例病例和2,144例对照 并查看906，000个基因突变，看看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，以确定那些风险最高的人， 脑出血和长期，以确定新的目标， 治疗和预防这种致命的中风亚型。

Abstract 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. Lay Summary 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.