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Stroke. 2015 Aug;46(8):2299-301. doi: 10.1161/STROKEAHA.115.009838. Epub 2015 Jun 25.

Rare Coding Variation and Risk of Intracerebral Hemorrhage.

Author information

1
From the Center for Human Genetic Research (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., M.R.R., J.R.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., M.R.R., J.R.), J. Philip Kistler Stroke Research Center (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., A.M.A., M.R.R., K.S., A.V., S.M.G., J.R.), and Department of Emergency Medicine (J.N.G.), Massachusetts General Hospital, Boston; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., M.R.R., J.R.); Department of Biostatistical Sciences, Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC (D.M., W.M.B., C.D.L.); Quinnipiac University, Frank H. Netter MD School of Medicine, Hamden, CT (W.J.D.); Department of Environmental Health (G.S., R.D.) and Department of Neurology and Rehabilitation (D.W.), University of Cincinnati College of Medicine, OH; Department of Neurology, Harborview Medical Center, University of Washington, Seattle (D.L.T.); Department of Neurology, University of Florida College of Medicine, Jacksonville (S.L.S.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA (M.S.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.F.M.); Department of Neurology, University of Michigan Health System, Ann Arbor (D.L.B.); and Departments of Neurology and Public Health Sciences, University of Virginia Health System, Charlottesville (B.B.W.).
2
From the Center for Human Genetic Research (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., M.R.R., J.R.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., M.R.R., J.R.), J. Philip Kistler Stroke Research Center (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., A.M.A., M.R.R., K.S., A.V., S.M.G., J.R.), and Department of Emergency Medicine (J.N.G.), Massachusetts General Hospital, Boston; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., M.R.R., J.R.); Department of Biostatistical Sciences, Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC (D.M., W.M.B., C.D.L.); Quinnipiac University, Frank H. Netter MD School of Medicine, Hamden, CT (W.J.D.); Department of Environmental Health (G.S., R.D.) and Department of Neurology and Rehabilitation (D.W.), University of Cincinnati College of Medicine, OH; Department of Neurology, Harborview Medical Center, University of Washington, Seattle (D.L.T.); Department of Neurology, University of Florida College of Medicine, Jacksonville (S.L.S.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA (M.S.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.F.M.); Department of Neurology, University of Michigan Health System, Ann Arbor (D.L.B.); and Departments of Neurology and Public Health Sciences, University of Virginia Health System, Charlottesville (B.B.W.). jrosand@partners.org.

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.

KEYWORDS:

apolipoproteins E; cerebral hemorrhage; genome-wide association study

PMID:
26111891
PMCID:
PMC4519408
DOI:
10.1161/STROKEAHA.115.009838
[Indexed for MEDLINE]
Free PMC Article

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