Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS)
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|ClinicalTrials.gov Identifier: NCT00682695|
Recruitment Status : Recruiting
First Posted : May 22, 2008
Last Update Posted : July 21, 2017
|Condition or disease|
The proposed research builds on the most robust, statistically significant and replicated association identified to determine the mechanism by which it may relate to ICH risk. Given that ICH is an extreme phenotype on a spectrum of manifestations of cerebral small vessel disease, the findings that emerge from our proposed studies offer the promise of broad impact for research and treatment in a wide variety of cerebrovascular disorders.
In the genetic epidemiology of hemorrhagic stroke, we propose to perform an in-depth fine-mapping of the entire 1q22 genomic region (~250kb) to investigate whether genetic variants influence gene expression that correlates with ICH status or changes in expression over time in ICH cases. As existing samples were not processed for gene expression analysis, we will recruit 500 non-lobar ICH cases (~150 black, ~350 white) and 1000 controls (300 black, 700 white) to correlate sequence variation with gene expression levels in the same samples. Identified associations will be replicated in 6,000 cases of ICH and 9,361 individuals in the CHARGE consortium with MRI white matter hyperintensity volume measurements and 5,000 controls. The current proposal takes the next logical step by pursuing the most promising findings of our GWAS to complete the following aims:
Specific Aim #1: Perform deep DNA sequencing of Chr 1q22 among non-Hispanic white and black ICH cases and controls to identify all genomic variation within these regions and test the following:
Hypothesis #1a: Variants strongly associated with ICH risk at 1q22 are either directly causal or in linkage disequilibrium to causal variants that influence ICH risk, and sequencing of these regions will reveal both common and rare variants that exert this causal influence.
Hypothesis #1b: Variants strongly associated with ICH risk at 1q22 will be associated with risk of, or severity of, leukoaraiosis.
Specific Aim #2: Prospectively collect DNA, RNA, and serum on ICH cases and geographic region site-specific controls both at the time of ICH and in the convalescent period. We will perform RNA expression profiling between cases and controls and over time in cases. We will compute expression quantitative trait locus (eQTL) analysis with SNPs arising from Aim 1. We will also determine whether alternatively spliced transcripts differ between cases and controls.
Hypothesis #2a: Variation in gene expression or alternatively spliced transcripts affects risk of ICH.
Hypothesis #2b: Variations identified by DNA sequencing will affect gene expression and/or alternatively spliced transcripts that affect risk of ICH.
|Study Type :||Observational|
|Estimated Enrollment :||1000 participants|
|Observational Model:||Ecologic or Community|
|Official Title:||Genetic and Environmental Risk Factors for Hemorrhagic Stroke|
|Study Start Date :||September 1997|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||June 2021|
Healthy volunteers and people who have had a hemorrhagic stroke and live within University of Maryland, University of Cincinnati, Massachusetts General Hospital and Duke University area
- Perform deep DNA sequencing of Chr 1q22 among non-Hispanic white and black ICH cases and controls to identify all genomic variation within these regions. [ Time Frame: Ongoing to be completed at the end of June 2021 ]
- Collect and analyze DNA, RNA, and serum on ICH cases and geographic region site-specific controls both at the time of ICH and in the convalescent period. We will perform RNA expression profiling between cases and controls and over time in cases. [ Time Frame: Ongoing to be completed at the end of June 2021 ]
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00682695
|Contact: Jennifer Osborne, RN, MSNfirstname.lastname@example.org|
|United States, Maryland|
|University of Maryland||Recruiting|
|Baltimore, Maryland, United States, 21201|
|Contact: Tiffany Watson 410-706-1902 email@example.com|
|Sub-Investigator: Steven Kittner, MD|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Christina Kourkoulis 617-726-5358|
|Sub-Investigator: Jonathan R, MD|
|United States, North Carolina|
|Durham, North Carolina, United States, 27710|
|Contact: Erlinda Yeh 919-681-4054 firstname.lastname@example.org|
|Sub-Investigator: Michael L James, MD|
|United States, Ohio|
|Cincinnati, Ohio, United States, 45267|
|Principal Investigator:||Daniel Woo, MD||University of Cincinnati|