Ethnic/Racial Variation in Intracerebral Hemorrhage (ERICH)

描述(申请人提供)：脑出血(ICH)是指脑实质内的血管破裂，导致神经损伤并经常死亡。大约40%-50%的脑出血患者将死于出血。在幸存者中，大多数是残疾人。因此，脑出血是发病率和死亡率最高的中风亚型。研究发现，非洲裔美国人和西班牙裔少数族裔的ICH发病率大约是白人的两倍，平均而言，ICH的年龄更小。然而，尽管医疗保健负担不成比例，但收集到的可用于检测的DNA在非裔美国人中不到200例，在西班牙裔中不到100例。我们的建议是在白人中收集1000例脑出血病例，在黑人中收集1000例脑出血病例，在西班牙裔中收集1000例脑出血病例，并收集按种族/民族、年龄(5岁)、性别和地理位置匹配的3000例对照。我们的长期目标是对脑出血进行全基因组相关性研究，其中包括相当大比例的少数族裔脑出血患者。一项全基因组关联研究用数十万个标记评估DNA，以确定与脑出血风险较高或较低相关的区域或基因。然而，目前的提案不会完成这类分析，因为目前没有足够的数字可用。因此，当前提案的目标是：1)了解黑人和拉美裔美国人中对脑出血最重要的风险因素；2)确定种族/族裔在脑成像方面的差异；3)确定调解种族/族裔预后差异的因素；以及4)确定拉美裔和非裔美国人是否来自不同地区或不同民族(如墨西哥、古巴等)。在基因上是不同的。为了实现这些目标，我们有11个招聘中心，代表全美30家招聘医院，其中有大量非裔美国人和拉美裔美国人。还将招募来自相同地区的白人脑出血病例，以说明风险因素的地区差异，以及风险因素、结果和成像差异的对照组。马萨诸塞州总医院将与乔治敦大学合作，开发一个集中的神经成像中心，用于统一阅读和分析电影。迈阿密人类基因组研究所将开发一个生物储存库，用于集中DNA处理和样本处理。维克森林大学将建立一个数据和统计中心。这项研究的主要优势是调查人员的经验，特别是在招募少数族裔人口和对非物质文化遗产和流行病学特别感兴趣的方面；对病例、风险因素和集中分析的统一定义；以及识别和招募研究所需的大量受试者(总计6000人)的能力。 公共卫生相关性：中风是第三大致死原因，也是成年人致残的首要原因。与阿尔茨海默氏症、心脏病、癌症或艾滋病相比，中风致残的人更多。脑出血是死亡率和致残率最高的中风类型。每年有70,000名美国人发生ICH，美国一年的ICH病例导致大约37亿美元的医疗费用。非洲裔美国人和西班牙裔美国人患这种中风的几率是白人的两倍，而且他们在较早的年龄就患有这种中风。然而，我们对导致这种种族差异的生物差异知之甚少。我们的建议将把患有ICH的少数族裔与来自相同人群的对照进行比较，并探索遗传， X线片和结果的差异。

DESCRIPTION (provided by applicant): Intracerebral hemorrhage (ICH) occurs when a blood vessel ruptures within the brain parenchyma leading to neurologic injury and frequently death. Approximately 40-50% of patients who suffer from an ICH will die from the hemorrhage. Of the survivors, the majority are disabled. Thus, ICH is the subtype of stroke with the highest morbidity and mortality rates. Minority populations of African-Americans and Hispanics have been found to have roughly double the rate of ICH as whites and on average, have ICH at a younger age. Yet despite this disproportionate health care burden, fewer than 200 ICH cases among African-Americans and less than a hundred ICH cases among Hispanics have been collected with DNA available for testing. Our proposal is to collect 1000 cases of ICH among whites, 1000 cases of ICH among blacks, 1000 cases of ICH among Hispanics, and 3000 controls matched to the cases by race/ethnicity, age (5 years), gender and geographic location. Our long-term goal is to perform a genome-wide association study of intracerebral hemorrhage which includes a significant proportion of minorities with ICH. A genome-wide association study evaluates DNA with hundreds of thousands of markers to identify regions or genes which are associated with either a greater or lesser risk of ICH. However, the current proposal will not complete this type of analysis as insufficient numbers are currently available. Thus, the goals of the current proposal are to: 1) understand the risk factors of greatest importance for ICH among blacks and Hispanics; 2) determine differences in brain-imaging by race/ethnicity; 3) determine factors that mediate differences in outcomes rates by race/ethnicity; and 4) determine if Hispanics and African-Americans from different regions or national origin (such as Mexican, Cuban, etc.) are genetically different. To accomplish these goals, we have 11 recruitment centers representing 30 recruitment hospitals throughout the United States with large populations of African-Americans and Hispanics. White ICH cases from the same regions will also be recruited to account for regional differences in risk factors as well as a comparison group for risk factors, outcomes and imaging differences. A centralized neuroimaging center will be developed for uniform reading and analysis of films at Massachusetts General Hospital in conjunction with Georgetown University. A biorepository will be developed for centralized DNA processing and sample handling at the Miami Institute for Human Genomics. And a data and statistical center will be developed at Wake Forest University. The major advantages of this study are the experience of the investigators, particularly with recruitment of minority populations and particular interest in ICH and epidemiology; uniform definitions of cases, risk factors, and centralized analyses; and the ability to identify and recruit the large number of subjects (6000 total) required for the study. PUBLIC HEALTH RELEVANCE: Stroke is the third leading cause of death and the leading cause of disability among adults. More people are disabled by stroke than Alzheimer's disease, heart disease, cancer or AIDS. Intracerebral hemorrhage is the type of stroke with the highest death and disability rates. ICH occurs in 70,000 Americans every year and a single year of ICH cases in the United States leads to approximately $3.7 billion dollars of health care costs. African-Americans and Hispanics have twice the rate of this type of stroke than whites do and have this type of stroke at an earlier age in life. Yet we know little about the biologic differences that lead to this ethnic disparity. Our proposal will compare minorities with ICH to controls from the same population as well as explore genetic, radiographic and outcomes differences.