Familial Aggregation of Stroke

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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.