Intracerebral hemorrhage (ICH) occurs when a blood vessel ruptures within the brain parenchyma leading to neurologic injury and frequently death. Approximately 40-50% of patients who suffer from an ICH will die from the hemorrhage. Of the survivors, the majority are disabled. Thus, ICH is the subtype of stroke with the highest morbidity and mortality rates. Minority populations of African-Americans and Hispanics have been found to have roughly double the rate of ICH as whites and on average, have ICH at a younger age. Yet despite this disproportionate health care burden, fewer than 200 ICH cases among African-Americans and less than a hundred ICH cases among Hispanics have been collected with DNA available for testing. Our proposal is to collect 1000 cases of ICH among whites, 1000 cases of ICH among blacks, 1000 cases of ICH among Hispanics, and 3000 controls matched to the cases by race/ethnicity, age (5 years), gender and geographic location. Our long-term goal is to perform a genome-wide association study of intracerebral hemorrhage which includes a significant proportion of minorities with ICH. A genome-wide association study evaluates DNA with hundreds of thousands of markers to identify regions or genes which are associated with either a greater or lesser risk of ICH. However, the current proposal will not complete this type of analysis as insufficient numbers are currently available. Thus, the goals of the current proposal are to: 1) understand the risk factors of greatest importance for ICH among blacks and Hispanics;2) determine differences in brain-imaging by race/ethnicity;3) determine factors that mediate differences in outcomes rates by race/ethnicity;and 4) determine if Hispanics and African-Americans from different regions or national origin (such as Mexican, Cuban, etc.) are genetically different. To accomplish these goals, we have 11 recruitment centers representing 30 recruitment hospitals throughout the United States with large populations of African-Americans and Hispanics. White ICH cases from the same regions will also be recruited to account for regional differences in risk factors as well as a comparison group for risk factors, outcomes and imaging differences. A centralized neuroimaging center will be developed for uniform reading and analysis of films at Massachusetts General Hospital in conjunction with Georgetown University. A biorepository will be developed for centralized DNA processing and sample handling at the Miami Institute for Human Genomics. And a data and statistical center will be developed at Wake Forest University. The major advantages of this study are the experience of the investigators, particularly with recruitment of minority populations and particular interest in ICH and epidemiology;uniform definitions of cases, risk factors, and centralized analyses;and the ability to identify and recruit the large number of subjects (6000 total) required for the study.

Public Health Relevance

Stroke is the third leading cause of death and the leading cause of disability among adults. More people are disabled by stroke than Alzheimer's disease, heart disease, cancer or AIDS. Intracerebral hemorrhage is the type of stroke with the highest death and disability rates. ICH occurs in 70,000 Americans every year and a single year of ICH cases in the United States leads to approximately $3.7 billion dollars of health care costs. African-Americans and Hispanics have twice the rate of this type of stroke than whites do and have this type of stroke at an earlier age in life. Yet we know little about the biologic differences that lead to this ethnic disparity. Our proposal will compare minorities with ICH to controls from the same population as well as explore genetic, radiographic and outcomes differences.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01NS069763-05
Application #
8738720
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Moy, Claudia S
Project Start
2010-08-01
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
5
Fiscal Year
2014
Total Cost
$6,022,206
Indirect Cost
$558,346
Name
University of Cincinnati
Department
Neurology
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Woo, Daniel; Kruger, Andrew J; Sekar, Padmini et al. (2016) Incontinence and gait disturbance after intraventricular extension of intracerebral hemorrhage. Neurology 86:905-11
Anderson, Christopher D; Falcone, Guido J; Phuah, Chia-Ling et al. (2016) Genetic variants in CETP increase risk of intracerebral hemorrhage. Ann Neurol 80:730-740
Walsh, Kyle B; Woo, Daniel; Sekar, Padmini et al. (2016) Untreated Hypertension: A Powerful Risk Factor for Lobar and Nonlobar Intracerebral Hemorrhage in Whites, Blacks, and Hispanics. Circulation 134:1444-1452
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Walsh, Kyle B; Woo, Daniel; Adeoye, Opeolu (2015) Response to Letter Regarding Article, ""Monocyte Count and 30-Day Case Fatality in Intracerebral Hemorrhage"". Stroke 46:e244
Walsh, Kyle B; Sekar, Padmini; Langefeld, Carl D et al. (2015) Monocyte Count and 30-Day Case Fatality in Intracerebral Hemorrhage. Stroke 46:2302-4
Darger, Bryan; Gonzales, Nicole; Banuelos, Rosa C et al. (2015) Outcomes of Patients Requiring Blood Pressure Control Before Thrombolysis with tPA for Acute Ischemic Stroke. West J Emerg Med 16:1002-6
Mackey, Jason; Brown, Robert D; Sauerbeck, Laura et al. (2015) Affected twins in the familial intracranial aneurysm study. Cerebrovasc Dis 39:82-6
Woo, Daniel; Falcone, Guido J; Devan, William J et al. (2014) Meta-analysis of genome-wide association studies identifies 1q22 as a susceptibility locus for intracerebral hemorrhage. Am J Hum Genet 94:511-21

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