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 #
1U01NS069208-01
Application #
7848501
Study Section
Special Emphasis Panel (ZNS1-SRB-G (40))
Program Officer
Corriveau, Roderick A
Project Start
2010-07-01
Project End
2014-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
1
Fiscal Year
2010
Total Cost
$3,690,607
Indirect Cost
Name
University of Maryland Baltimore
Department
Neurology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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Phuah, Chia-Ling; Dave, Tushar; Malik, Rainer et al. (2017) Genetic variants influencing elevated myeloperoxidase levels increase risk of stroke. Brain 140:2663-2672
Woo, Daniel; Debette, Stephanie; Anderson, Christopher (2017) 20th Workshop of the International Stroke Genetics Consortium, November 3-4, 2016, Milan, Italy: 2016.036 ISGC research priorities. Neurol Genet 3:S12-S18
Magvanjav, Oyunbileg; McDonough, Caitrin W; Gong, Yan et al. (2017) Pharmacogenetic Associations of ?1-Adrenergic Receptor Polymorphisms With Cardiovascular Outcomes in the SPS3 Trial (Secondary Prevention of Small Subcortical Strokes). Stroke 48:1337-1343
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(2017) 19th Workshop of the International Stroke Genetics Consortium, April 28-29, 2016, Boston, Massachusetts, USA: 2016.001 MRI-defined cerebrovascular genomics-The CHARGE consortium. Neurol Genet 3:S2-S11
Biffi, Alessandro; Bailey, Destiny; Anderson, Christopher D et al. (2016) Risk Factors Associated With Early vs Delayed Dementia After Intracerebral Hemorrhage. JAMA Neurol 73:969-76
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
Keenan, Tanya; Zhao, Wei; Rasheed, Asif et al. (2016) Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study. J Am Coll Cardiol 67:407-416

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