Platform for Accelerating Genetic Discovery for Cerebrovascular Disease

Broad Institute, Inc., Cambridge MA

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): Despite substantial advances in its treatment and prevention, stroke remains the second-leading cause of death worldwide and the leading cause of major disability among adults. Identifying the biological processes that underlie the cerebrovascular diseases that cause stroke is crucial to guiding the development of safe and effective therapies. The dramatic fall in cost of genome-wide genotyping and sequencing has made it possible to systematically collect vast amounts of data on individual genome variation. In parallel with advances in genotyping and sequencing technology, there has been a substantial increase in the availability and complexity of data characterizing patients. Neuroimaging, via CT and often MRI, is very frequently obtained during routine clinical evaluation and classification of stroke subtype can now be comprehensively ascertained using online tools that require and retain large amounts of primary data from medical evaluations. Finally, electronic medical records now retain increasing amounts of data on patients enrolled in research studies. By generating and analyzing genome-wide genotypes and collecting and analyzing extensive imaging and phenotype data in thousands of individuals with stroke, the International Stroke Genetics Consortium (ISGC) has made substantial progress in identifying the genetic variants that influence risk of stroke, the initial step in the discovery cycle. Nonetheless, substantial barriers remain to leveraging these and future data for the advancement of our understanding of cerebrovascular disease and the ultimate development of novel therapeutic targets for stroke. Datasets are (1) of unprecedented scale, (2) disparate in location, and (3) heterogeneous in type. As a result, the research community lacks the data access and integration necessary in order to perform valid and well-powered comparisons to generate new hypotheses and improve our understanding of cerebrovascular disease biology. We propose to create new infrastructure for the wide sharing of human genetic, phenotypic and neuroimaging data for the purpose of accelerating the search for effective treatments for cerebrovascular disease. The Platform for accelerating genetic discovery for cerebrovascular disease will overcome these three barriers by creating a flexible and scalable resource for the investigative community that integrates genetic datasets containing individual-level genotyping results, incorporating over 30,000 stroke cases and appropriate stroke- free controls collected from dozens of centers around the world, all having undergone centralized quality control according to a single streamlined approach, and all made available through an ethics committee- approved process for rapid sharing with any investigator world-wide. Governed by a steering committee made up of long-standing collaborators in stroke genetics, this resource will transform the genetic study of stroke in humans, providing a durable resource that can ultimately be sustained by the established collaborative culture of the ISGC and small subsidies from researchers who utilize the Platform