Rare Coding Variation and Risk of Intracerebral Hemorrhage
Year: 2015
Type: article
Study design: Observational Study
Abstract: BACKGROUND AND PURPOSE: Intracerebral hemorrhage has a substantial genetic component. We performed a preliminary search for rare coding variants associated with intracerebral hemorrhage. METHODS: A total of 757 cases and 795 controls were genotyped using the Illumina HumanExome Beadchip (Illumina, Inc, San Diego, CA). Meta-analyses of single-variant and gene-based association were computed. RESULTS: No rare coding variants were associated with intracerebral hemorrhage. Three common variants on chromosome 19q13 at an established susceptibility locus, encompassing TOMM40, APOE, and APOC1, met genome-wide significance (P<5e-08). After adjusting for the APOE epsilon alleles, this locus was no longer convincingly associated with intracerebral hemorrhage. No gene reached genome-wide significance level in gene-based association testing. CONCLUSIONS: Although no coding variants of large effect were detected, this study further underscores a major challenge for the study of genetic susceptibility loci; large sample sizes are required for sufficient power except for loci with large effects.
Source: Stroke
Authors: Farid Radmanesh, Guido J. Falcone, Christopher D. Anderson, David McWilliams, William J. Devan, W. Mark Brown, Thomas W.K. Battey, Alison M. Ayres, Miriam R. Raffeld, Kristin Schwab, Guangyun Sun, Ranjan Deka, Anand Viswanathan, Joshua N. Goldstein, Steven M. Greenberg, David L. Tirschwell, Scott L. Silliman, Magdy Selim, James F. Meschia, Devin L. Brown, Bradford B. Worrall, Carl D. Langefeld, Daniel Woo, Jonathan Rosand
Institutions: Broad Institute, Beth Israel Deaconess Medical Center, Mayo Clinic, University of Washington, University of Virginia Health System, Harborview Medical Center, University of Florida, Michigan Medicine, Mayo Clinic in Florida, Quinnipiac University, Wake Forest University Health Sciences, Wake Forest University, University of Cincinnati
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1002485965, Genetic and Environmental Risk Factors for Hemorrhagic Stroke, SCORE-IT: The CTA Spot Sign Score in Acute Cerebral Hemorrhage, G478511654, Genetic Determinants of Hematoma Volume, Gene Discovery for Warfarin-Related Intracerebral Hemorrhage, Massachusetts Alzheimer's Disease Research Center, Predictors of hematoma expansion in acute intracerebral hemorrhage, Massachusetts Alzheimer's Disease Research Center (MADRC), Genetic Analyses of Lipids in Cerebral Hemorrhage and Small Vessel Disease
OpenAlex ID: W2154242866