Evidence map›Paper›PMID 25953367›Full record

Trial reportStroke2015

Common NOTCH3 Variants and Cerebral Small-Vessel Disease.

Loes C A Rutten-Jacobs, Matthew Traylor, Poneh Adib-Samii, Vincent Thijs, Cathie Sudlow, Peter M Rothwell, Giorgio Boncoraglio, Martin Dichgans, Steve Bevan, James Meschia and 5 more

Abstract readClinical TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Stroke, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 3 pooled it
–field-weighted citation impact
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

14 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Neurology · 2017
    Pooled it
  4. NOTCH3 variants of unknown significance underpin vascular dysfunction in neurodegenerative disease: a case series of three nfvPPA-FTD patients.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Article
  5. Multimodal neuroimaging ofFrontiers in neuroscience · 2025
    Article
  6. Impaired intracellular CaScience signaling · 2023
    Article
  7. Headache andNeurology international · 2023
    Article
  8. Elevated TGFβ signaling contributes to cerebral small vessel disease in mouse models of Gould syndrome.Matrix biology : journal of the International Society for Matrix Biology · 2023
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
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

15 authors.

Loes C A Rutten-JacobsFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.). LR406@medschl.cam.ac.uk.
Matthew TraylorFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).
Poneh Adib-SamiiFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).
Vincent ThijsFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).
Cathie SudlowFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).
Peter M RothwellFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).
Giorgio BoncoraglioFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).
Martin DichgansFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).
Steve BevanFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).
James MeschiaFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).
Christopher LeviFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).
Natalia S RostFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).
Jonathan RosandFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).
Ahamad HassanFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).
Hugh S MarkusFrom the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (L.C.A.R.-J., M.T., S.B., H.S.M.); Stroke and Dementia Research Center, Department of Clinical Neuroscience, St George's University of London, London, United Kingdom (P.A.-S.); Department of Experimental Neurology, KULeuven and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium (V.T.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy (G.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich, Munich, Germany (M.D.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.M.); Center for Clinical Epidemiology and Biostatistics, Department of Neurology, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia (C.L.); Department of Neurology, Center for Human Genetic Research and Massachusetts General Hospital, Boston (N.S.R., J.R.); and Department of Neurology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom (A.H.).

Funding

The NINDS International Stroke Genetics Consortium StudyU01NS069208 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI KITTNER, STEVEN J · 2010 to 2013
$9.4M
Statins augment small vessel function and improve stroke outcomesR01NS082285 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ROST, NATALIA S · 2013 to 2017
$2.6M
British Heart Foundation BHF 2010/01Medical Research Council G0900295NINDS NIH HHS R01 NS082285-01NINDS NIH HHS U01 NS069208Wellcome Trust 072952Wellcome Trust 095626
6 · The paper itself

Abstract

background and purposeThe most common monogenic cause of cerebral small-vessel disease is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, caused by NOTCH3 gene mutations. It has been hypothesized that more common variants in NOTCH3 may also contribute to the risk of sporadic small-vessel disease. Previously, 4 common variants (rs10404382, rs1043994, rs10423702, and rs1043997) were found to be associated with the presence of white matter hyperintensity in hypertensive community-dwelling elderly.

methodsWe investigated the association of common single nucleotide polymorphisms (SNPs) in NOTCH3 in 1350 patients with MRI-confirmed lacunar stroke and 7397 controls, by meta-analysis of genome-wide association study data sets. In addition, we investigated the association of common SNPs in NOTCH3 with MRI white matter hyperintensity volumes in 3670 white patients with ischemic stroke. In each analysis, we considered all SNPs within the NOTCH3 gene, and within 50-kb upstream and downstream of the coding region. A total of 381 SNPs from the 1000 genome population with a mean allele frequency>0.01 were included in the analysis. A significance level of P<0.0015 was used, adjusted for the effective number of independent SNPs in the region using the Galwey method.

resultsWe found no association of any common variants in NOTCH3 (including rs10404382, rs1043994, rs10423702, and rs1043997) with lacunar stroke or white matter hyperintensity volume. We repeated our analysis stratified for hypertension but again found no association.

conclusionsOur study does not support a role for common NOTCH3 variation in the risk of sporadic small-vessel disease.

Indexed as

AllelesGene FrequencyPolymorphism, Single NucleotideFemaleGenome-Wide Association StudyHumansHypertensionMaleMiddle AgedReceptor, Notch3Receptors, NotchStroke, LacunarNOTCH3 protein, humanReceptor, Notch3Receptors, NotchCADASILcerebral small vessel diseasesgenetic association studiesstroke, lacunar

Identifiers

PMID25953367
PMCPMC4442025

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