Evidence map›Paper›PMID 26718567›Full record

ArticleNeurology2016

Shared genetic susceptibility of vascular-related biomarkers with ischemic and recurrent stroke.

Stephen R Williams, Fang-Chi Hsu, Keith L Keene, Wei-Min Chen, Sarah Nelson, Andrew M Southerland, Ebony B Madden, Bruce Coull, Stephanie M Gogarten, Karen L Furie and 12 more

Open access · bronzeAbstract read
In one paragraph

Article in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 4 pooled it
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 4 syntheses or guidelines pooled it, 40 citations in OpenAlex.

  1. Pooled it
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  4. Promoter Polymorphism (-174, G/C) of Interleukin-6 and Arterial Thromboembolic Events: A Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2016
    Pooled it
  5. Trial
  6. Observational
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 10 institutions in 3 countries.

Stephen R WilliamsFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Fang-Chi HsuFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Keith L KeeneFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Wei-Min ChenFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Sarah NelsonFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Andrew M SoutherlandFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Ebony B MaddenFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Bruce CoullFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Stephanie M GogartenFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Karen L FurieFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Godfrey DzhivhuhoFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Joe L RowlesFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Prachi MehndirattaFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Rainer MalikFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Josée DupuisFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Honghuang LinFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Sudha SeshadriFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Stephen S RichFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Michèle M SaleFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA.
Bradford B WorrallFrom the Center for Public Health Genomics (S.R.W., K.L.K., W.-M.C., S.S.R., M.M.S.), Cardiovascular Research Center (S.R.W.), and Departments of Public Health Sciences (A.M.S., B.B.W.), Neurology (P.M., B.B.W.), Medicine (M.M.S.), Biochemistry and Molecular Genetics (M.M.S.), and Public Health Sciences (S.S.R.), University of Virginia, Charlottesville; Department of Biostatistical Sciences (F.-C.H.), Wake Forest School of Medicine, Winston-Salem, NC; National Human Genome Research Institute (E.B.M.), Bethesda, MD; Departments of Neurology (A.M.S., K.L.F.) and Neuroscience (K.L.F.), Brown University, Providence, RI; Department of Neurology (B.C.), University of Arizona, Tucson; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Biostatistics (S.N., S.M.G.), University of Washington, Seattle; Department of Clinical Laboratory Sciences (G.D.), University of Cape Town, South Africa; Department of Biochemistry (J.L.R.), University of Missouri, Columbia; Institute for Stroke and Dementia Research (R.M.), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Biostatistics (J.D.), Boston University School of Public Health; and Departments of Neurology (S.S.) and Medicine (H.L.), Boston University School of Medicine, MA. bbw9r@virginia.edu.
METASTROKE, The Genomics and Randomized Trials Network (GARNET) Collaborative Research Group
METASTROKE The Genomics and Randomized Trials Network GARNET Collaborative Research Group
Boston University · USUniversity of Arizona · USBrown University · USUniversity of Missouri · USUniversity of Cape Town · ZAEast Carolina University · USLudwig-Maximilians-Universität München · DENational Human Genome Research Institute · USUniversity of Washington · USWake Forest University · US

Funding

PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9M
Vitamin Intervention for Stroke Prevention (VISP)R01NS034447 · NINDS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI TOOLE, JAMES F · 1996 to 2006
$18.0M
EPIDEMIOLOGY OF DEMENTIA IN THE FRAMINGHAM STUDYR01AG008122 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI AU, RHODA, SESHADRI, SUDHA · 1989 to 2015
$14.4M
Temporal Trends, Novel Imaging and Molecular Characterization of Preclinical and Clinical Alzheimer's Disease in the Framingham CohortsR01AG054076 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI DECARLI, CHARLES, SESHADRI, SUDHA · 2016 to 2020
$12.3M
ARIC Neurocognitive Study (ARIC-NCS) Renewal 2 of 5U01HL096917 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI MOSLEY, THOMAS H · 2010 to 2018
$11.9M
Collaborative GWAS of Dementia, AD and related MRI and Cognitive EndophenotypesR01AG033193 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SESHADRI, SUDHA · 2009 to 2016
$4.4M
Randomized Clinical Trials - Whole Genome Studies Coordinating CenterU01HG005157 · NHGRI · UNIVERSITY OF WASHINGTON · PI HEAGERTY, PATRICK J, WEIR, BRUCE S. · 2009 to 2011
$2.4M
TARGETING OF SELECTABLE MARKERS TO ANY GENETIC LOCUSR43HG000443 · NHGRI · INTEGRATED GENETICS, INC. · PI LANDES, GREG M · 1990 to 1990
–
THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195N01HC025195 · HC · TRUSTEES OF BOSTON UNIVERSITY · PI WOLF, PHILIP A · 2002 to 2006
–
NHGRI NIH HHS U01 HG004438LNHGRI NIH HHS U01HG005157NHGRI NIH HHS U01HG00516-03NHLBI NIH HHS N01-HC-25195NHLBI NIH HHS U01HL 096917NIA NIH HHS AG033193NIA NIH HHS AG08122NINDS NIH HHS NS17950NINDS NIH HHS R01 NS34447
6 · The paper itself

Abstract

objectiveTo investigate the genetic contributors to cerebrovascular disease and variation in biomarkers of ischemic stroke.

methodsThe Vitamin Intervention for Stroke Prevention Trial (VISP) was a randomized, controlled clinical trial of B vitamin supplementation to prevent recurrent stroke, myocardial infarction, or death. VISP collected baseline measures of C-reactive protein (CRP), fibrinogen, creatinine, prothrombin fragments F1+2, thrombin-antithrombin complex, and thrombomodulin prior to treatment initiation. Genome-wide association scans were conducted for these traits and follow-up replication analyses were performed.

resultsWe detected an association between CRP single nucleotide polymorphisms (SNPs) and circulating CRP levels (most associated SNP, rs2592902, p = 1.14 × 10(-9)) in 2,100 VISP participants. We discovered a novel association for CRP level in the AKR1D1 locus (rs2589998, p = 7.3 × 10(-8), approaching genome-wide significance) that also is an expression quantitative trait locus for CRP gene expression. We replicated previously identified associations of fibrinogen with SNPs in the FGB and LEPR loci. CRP-associated SNPs and CRP levels were significantly associated with risk of ischemic stroke and recurrent stroke in VISP as well as specific stroke subtypes in METASTROKE. Fibrinogen levels but not fibrinogen-associated SNPs were also found to be associated with recurrent stroke in VISP.

conclusionsOur data identify a genetic contribution to inflammatory and hemostatic biomarkers in a stroke population. Additionally, our results suggest shared genetic contributions to circulating CRP levels measured poststroke and risk for incident and recurrent ischemic stroke. These data broaden our understanding of genetic contributors to biomarker variation and ischemic stroke risk, which should be useful in clinical risk evaluation.

Indexed as

BiomarkersGenetic Predisposition to DiseaseGenome-Wide Association StudyAgedBrain IschemiaC-Reactive ProteinFemaleFibrinogenGene ExpressionGenetic LociHumansMaleMiddle AgedOxidoreductasesPolymorphism, Single NucleotideRandomized Controlled Trials as Topic3-oxo-5 beta-steroid delta 4-dehydrogenaseBiomarkersC-Reactive ProteinFibrinogenOxidoreductases

Identifiers

PMID26718567
PMCPMC4776093
OpenAlexW2302154415

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.