Intracerebral hemorrhage (ICH) is the subtype of stroke with the highest disability and mortality rates. Half of the mortality occurs in the first 2 days after stroke;making prevention of paramount importance. This competitive renewal builds upon the collection of cases of hemorrhagic stroke and population-based controls over the past eight years. Despite evidence for a genetic component for ICH, no genome-wide linkage studies for common forms of ICH have been performed. This is likely because of the late onset and high mortality rate which makes identifying living affected relative pairs difficult. Our long- term goal is to identify new risk factors and treatments to prevent ICH. Thus, we propose to perform a genome-wide association study of 1,072 cases of ICH compared to 2,144 population-based, demographically matched controls using the Affymetrix 6.0 Chip. Our preliminary data includes actual genotyping using buccal swabs from the early part of our study as well as blood samples and data on the recruitment rate using the methods proposed. Our primary hypothesis is that specific SNPs will be associated with ICH independent of traditional risk factors including hypertension, diabetes, smoking, alcohol use and Apolipoprotein E alleles. Our center is uniquely positioned to efficiently and economically perform a genome-wide association study with controls that have been randomly selected from the population, drawn from the same population as cases and because of the population-based nature of the study, provide an estimate of how important a risk factor may be to the overall incidence of ICH. Our center has a well- established phenotyping methodology and brings experts to each stage of the study design, methodology and analysis.

Public Health Relevance

Intracerebral hemorrhage is a type of stroke where blood vessels rupture in the brain. Of the subtypes of stroke, it has the highest rates of death and disability and while treatments are being developed, the best defense is to prevent intracerebral hemorrhage. Our study examines a total of 1,072 cases and 2,144 controls from the same population as the cases and looks at 906,000 genetic mutations to see if any of them are associated with intracerebral hemorrhage. In the short-term, our findings may lead to identification of tests that can be performed to identify those at highest risk for intracerebral hemorrhage and in the long-term, to the identification of novel targets for treatment and prevention of this deadly subtype of stroke.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS036695-13
Application #
8073025
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Gwinn, Katrina
Project Start
1997-09-12
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
13
Fiscal Year
2011
Total Cost
$1,631,732
Indirect Cost
Name
University of Cincinnati
Department
Neurology
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Marini, Sandro; Devan, William J; Radmanesh, Farid et al. (2018) 17p12 Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage. Stroke 49:1618-1625
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Radmanesh, Farid; Falcone, Guido J; Anderson, Christopher D et al. (2015) Rare Coding Variation and Risk of Intracerebral Hemorrhage. Stroke 46:2299-301

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