Familial Aggregation of Stroke

描述(由申请者提供)：此建议书针对的是被指导者 PatientOriented Research职业发展奖。我的长期目标是学习 中风的遗传流行病学作为独立的调查者。作为人类 基因组计划接近完成，单核苷酸的数量 可用于连锁分析的多态接近30万， 需要能够弥合分子间信息鸿沟的科学家 遗传学和临床医学变得越来越重要。中风是一种 尤其是具有不同遗传和环境的复杂疾病 对笔划和笔划子类型的影响，使解剖复杂化 这一特点。中风临床领域的专业知识是先决条件，但 就其本身而言，不足以适当地寻找各种 笔划子类型。 在未来，我计划独立设计、管理和分析 探索卒中遗传和环境因素的复杂关系 和笔划子类型。为了实现这一目标，我将获得理科硕士学位 在分子遗传学方面以及在统计学方面进行广泛的培训 遗传学和计算机科学是当代科学的一个组成部分 统计学和遗传学。这项研究项目被设计成一种工具 了解遗传流行病学、数据获取和 对结果的分析，以及从以下方面引起的实验困难 基于群体的遗传学研究。这些工具对于设计是必不可少的， 遗传流行病学研究的管理和分析。此外， 研究项目将提供一个关于家庭和基因的数据库 材料来自脑内出血的家族聚集物，这将是 为今后的研究奠定了基础。 研究项目的具体目标是：1)确定比例 家族性脑出血(ICH) 控制环境危险因素后卒中的聚集；2) 确定脑出血部位(叶与非叶)对脑出血风险的重要性 卒中的家族聚集性；3)确定脑出血的危险比。 病例的一级亲属与对照的比较 先证者。确定脑出血家族聚集性的组成部分，即 与环境风险因素的家族聚集性无关的是 中风遗传流行病学分析的基本步骤。

DESCRIPTION (provided by applicant): This proposal is for a Mentored PatientOriented Research Career Development Award. My longterm goal is to study the genetic epidemiology of stroke as an independent investigator. As the human genome project nears completion and the number of single nucleotide polymorphisms that can be used for linkage analysis approaches 300,000, the need for scientists that can bridge the information gap between molecular genetics and clinical medicine becomes increasingly important. Stroke is a particularly complex disease that has varying genetic and environmental influences for both stroke and stroke subtypes that complicates the dissection of the trait. Expertise in the clinical field of stroke is a prerequisite, but by itself, inadequate to properly search for the genetic roots of the various stroke subtypes. In the future, I plan to independently design, manage and analyze studies that explore the complex relationship of genetic and environmental causes of stroke and stroke subtypes. To achieve this goal, I will obtain a masters of Science in Molecular Genetics as well as undertake extensive training in statistical genetics and in the computer science that is an integral part of current statistics and genetics. The research project is designed to be a vehicle for understanding the complexities of genetic epidemiology, data acquisition and analysis of results, and experimental difficulties that arise from populationbased genetic studies. These tools are essential for the design, management and analysis of a genetic epidemiology study. In addition, the research project will provide a database of families as well as genetic material from familial aggregations of intracerebral hemorrhage, which will be the foundation of future studies. The specific aims of the research project are: 1) to determine the proportion of cases of intracerebral hemorrhage (ICH) attributable to the familial aggregation of stroke after controlling for environmental risk factors; 2) to determine the importance of location (lobar vs. nonlobar) of ICH to the risk of familial aggregation of stroke; and 3) to determine the risk ratio for ICH in first degree relatives of cases as compared to controls by relationship to the proband. Determining the component of the familial aggregation of ICH that is independent of the familial aggregation of environmental risk factors is a fundamental step in the analysis of the genetic epidemiology of stroke.