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.
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.
|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|
|Malik, Rainer; Bevan, Steve; Nalls, Michael A et al. (2014) Multilocus genetic risk score associates with ischemic stroke in case-control and prospective cohort studies. Stroke 45:394-402|
|Biffi, Alessandro; Sabuncu, Mert R; Desikan, Rahul S et al. (2014) Genetic variation of oxidative phosphorylation genes in stroke and Alzheimer's disease. Neurobiol Aging 35:1956.e1-8|
|Dichgans, Martin; Malik, Rainer; König, Inke R et al. (2014) Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants. Stroke 45:24-36|
|Ay, Hakan; Arsava, Ethem Murat; Andsberg, Gunnar et al. (2014) Pathogenic ischemic stroke phenotypes in the NINDS-stroke genetics network. Stroke 45:3589-96|
|McArdle, Patrick F; Kittner, Steven J; Ay, Hakan et al. (2014) Agreement between TOAST and CCS ischemic stroke classification: the NINDS SiGN study. Neurology 83:1653-60|
|Dalca, Adrian Vasile; Sridharan, Ramesh; Cloonan, Lisa et al. (2014) Segmentation of cerebrovascular pathologies in stroke patients with spatial and shape priors. Med Image Comput Comput Assist Interv 17:773-80|
|Meschia, J F (2014) GLA mutation as a risk factor for later life small vessel ischaemic disease. Eur J Neurol 21:3-4|
|Rundek, Tatjana; Brown, Devin L (2014) Socioeconomic status and subclinical atherosclerosis: are we closing disparity gaps? Stroke 45:948-9|
|Cheng, Yu-Ching; Cole, John W; Kittner, Steven J et al. (2014) Genetics of ischemic stroke in young adults. Circ Cardiovasc Genet 7:383-92|
Showing the most recent 10 out of 43 publications