The long-term objective of this application is to characterize the genetic basis for stroke susceptibility in order to develop more effective prevention and treatment strategies. Our study will thoroughly test the hypothesis that common variants play a major role in stroke, setting the stage for the future genetic study of this disease. This proposal builds on the innovative collaborative network established by the International Stroke Genetics Consortium (ISGC). For the present proposal, ISGC members from the USA have formed a smaller consortium, which includes the following studies: Baltimore-Washington Young Stroke Study, Siblings with Ischemic Stroke Study, Ischemic Stroke Genetics Study, Greater Cincinnati/Northern Kentucky Stroke Study, Northern Manhattan Study, Genes Affecting Stroke Risk and Outcome Study/Bugher Network Study, Heart and Vascular Health Stroke Study, Reasons for Geographic and Racial Differences in Stroke, Nurses Health Study, and Women's Health Initiative.
Our specific aims are to: 1. Assemble ischemic stroke phenotypic data and either high quality DNA samples or genotype data from 10 stroke studies with access to 7,033 cases of ischemic stroke and 23,411 study-specific controls. Phenotype data will be harmonized and new genome-wide genotyping will be performed on an estimated 4,420 cases and 3,277 controls. 2. Test for associations with ischemic stroke, rigorously categorized according to subtypes, within this 10-study consortium. Study-specific analyses will be performed and these results will be combined for a metaanalysis of ischemic stroke and its subtypes, with secondary analyses addressing subpopulations, including race/ethnicity, gender, and age of onset. 3. Replicate and extend associations detected in Aim 2 above by taking advantage of other genome-wide association studies conducted by members of the ISGC, including the Wellcome Trust Case-Control Consortium, the Australian National Research Council Study, and the Cohorts for Heart and Aging Research in Genomic Epidemiology.

Public Health Relevance

Stroke, defined as acute vascular disease of the brain, is the third leading cause of death and the leading cause of major disability. The long-range goal of our research is to characterize the genetic basis for stroke susceptibility in order to develop the effective prevention and treatment strategies that are desperately needed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01NS069208-04
Application #
8479450
Study Section
Special Emphasis Panel (ZNS1-SRB-G)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$676,808
Indirect Cost
$42,446
Name
University of Maryland Baltimore
Department
Type
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Cheng, Yu-Ching; Stanne, Tara M; Giese, Anne-Katrin et al. (2016) Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2. Stroke 47:307-16
Holliday, Elizabeth G; Traylor, Matthew; Malik, Rainer et al. (2015) Genetic overlap between diagnostic subtypes of ischemic stroke. Stroke 46:615-9
Raffeld, Miriam R; Biffi, Alessandro; Battey, Thomas W K et al. (2015) APOE ε4 and lipid levels affect risk of recurrent nonlobar intracerebral hemorrhage. Neurology 85:349-56
Rutten-Jacobs, Loes C A; Traylor, Matthew; Adib-Samii, Poneh et al. (2015) Common NOTCH3 Variants and Cerebral Small-Vessel Disease. Stroke 46:1482-7
Malik, Rainer; Freilinger, Tobias; Winsvold, Bendik S et al. (2015) Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants. Neurology 84:2132-45
Battey, Thomas W K; Valant, Valerie; Kassis, Sylvia Baedorf et al. (2015) Recommendations from the international stroke genetics consortium, part 2: biological sample collection and storage. Stroke 46:285-90
NINDS Stroke Genetics Network (SiGN); International Stroke Genetics Consortium (ISGC) (2015) Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study. Lancet Neurol :
Cole, John W; Xu, Huichun (2015) Aryl Hydrocarbon Receptor Repressor Methylation: A Link Between Smoking and Atherosclerosis. Circ Cardiovasc Genet 8:640-2
Carty, Cara L; Keene, Keith L; Cheng, Yu-Ching et al. (2015) Meta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans. Stroke 46:2063-8
Shah, Jay; Poonawala, Husain; Keay, Susan K et al. (2015) Varicella-Zoster Virus Vasculopathy: A Case Report Demonstrating Vasculitis using Black-Blood MRI. J Neurol Neurophysiol 6:

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