Evidence map›Paper›PMID 32517579›Full record

SynthesisStroke2020

Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities.

Nicola J Armstrong, Karen A Mather, Muralidharan Sargurupremraj, Maria J Knol, Rainer Malik, Claudia L Satizabal, Lisa R Yanek, Wei Wen, Vilmundur G Gudnason, Nicole D Dueker and 76 more

Open access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Stroke, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
13.1field-weighted citation impact, top 1% 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

67 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Unravelling the genetic architecture of cerebral small vessel disease in the context of stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. White matter hyperintensity spatial patterns: Risk factors and clinical correlates.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  12. Article
  13. Review
  14. The genetic and environmental etiology of novel frequency-driven regional parcellations of abnormal white matter.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2025
    Article
  15. Article
  16. Article
  17. Article
  18. The MIND diet, brain transcriptomic alterations, and dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  19. Article
  20. Review

7 more citing papers are in PubMed but not listed here.

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

86 authors at 20 institutions in 10 countries.

Nicola J ArmstrongMathematics and Statistics, Murdoch University, Perth, Australia (N.J.A.).
Karen A MatherCentre for Healthy Brain Ageing, School of Psychiatry (K.A.M., W.W., H.B., J.J., A.T., J.T., P.S.S.), University of New South Wales, Sydney, Australia.
Muralidharan SargurupremrajUniversity Bordeaux, Inserm, Bordeaux Population Health Research Center, France (M.S., C.T., S.D.).
Maria J KnolDepartment of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (M.J.K., D.V., N.A., G.V.R., M.W.V., C.M.v.D., M.A.I., H.H.H.A.).
Rainer MalikInstitute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-Universität LMU Munich, Germany (R.M., M.D.).
Claudia L SatizabalGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX (C.L.S., S.S.).
Lisa R YanekGeneSTAR Research Program (L.R.Y., B.G.K., L.C.B., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.
Wei WenCentre for Healthy Brain Ageing, School of Psychiatry (K.A.M., W.W., H.B., J.J., A.T., J.T., P.S.S.), University of New South Wales, Sydney, Australia.
Vilmundur G GudnasonIcelandic Heart Association, Kopavogur (V.G.G., S.S.).
Nicole D DuekerDr. John T. Macdonald Foundation Department of Human Genetics (R.L.S.), University of Miami, FL.
Lloyd T ElliottDepartment of Statistics and Actuarial Science, Simon Fraser University, Burnaby, BC, Canada (L.T.E.).
Edith HoferClinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Austria (E.H., R.S.).
Joshua BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA (J.B., B.P., W.L.).
Neda JahanshadMark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Marina del Rey (N.J., P.M.T.).
Shuo LiDepartment of Biostatistics, Boston University School of Public Health, Boston, MA (S.L., M.A.L., A.S.B., Q.Y.).
Mark A LogueDepartment of Psychiatry and Biomedical Genetics Section (M.A.L.), Boston University School of Medicine, MA.
Michelle LucianoCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, United Kingdom (M.L., I.J.D., D.C.M.L., M.E.B., J.M.W.).
Markus ScholzInstitute for Medical Informatics, Statistics and Epidemiology (M.S.).
Albert V SmithUniversity of Iceland, Reykjavik, Iceland (V.G.G., A.V.S.).
Stella TrompetDepartment of Internal Medicine, Section of Gerontology and Geriatrics (S.T.), Leiden University Medical Center, the Netherlands.
Dina VojinovicDepartment of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (M.J.K., D.V., N.A., G.V.R., M.W.V., C.M.v.D., M.A.I., H.H.H.A.).
Rui XiaBrown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, TX (R.X., M.F.).
Fidel Alfaro-AlmagroWellcome Centre for Integrative Neuroimaging (WIN FMRIB) (L.T.E., F.A.-A., L.G., M.J., S.M.S.), University of Oxford, United Kingdom.
David AmesNational Ageing Research Institute, Parkville, Victoria, Australia (D.A.).
Najaf AminDepartment of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (M.J.K., D.V., N.A., G.V.R., M.W.V., C.M.v.D., M.A.I., H.H.H.A.).
Philippe AmouyelLille University, Inserm, Institut Pasteur de Lille, RID-AGE - Risk Factors and Molecular Determinants of Aging-Related Diseases and Labex Distalz, France (P.A.).
Alexa S BeiserThe Framingham Heart Study, MA (C.L.S., A.S.B., J.R.R., S.S.).
Henry BrodatyCentre for Healthy Brain Ageing, School of Psychiatry (K.A.M., W.W., H.B., J.J., A.T., J.T., P.S.S.), University of New South Wales, Sydney, Australia.
Ian J DearyCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, United Kingdom (M.L., I.J.D., D.C.M.L., M.E.B., J.M.W.).
Christine Fennema-NotestineDepartment of Psychiatry (C.F.-N.), University of California, San Diego, La Jolla, CA.
Piyush G GampawarGottfried Schatz Research Center (for Cell Signaling, Metabolism and Aging), Medical University of Graz, Austria (P.G.G., H.S.).
Rebecca GottesmanDepartment of Neurology, Cerebrovascular and stroke Division (R.G.), Johns Hopkins University School of Medicine, Baltimore, MD.
Ludovica GriffantiWellcome Centre for Integrative Neuroimaging (WIN FMRIB) (L.T.E., F.A.-A., L.G., M.J., S.M.S.), University of Oxford, United Kingdom.
Clifford R JackDepartment of Radiology, Mayo Clinic, Rochester, MN (C.R.J.J.).
Mark JenkinsonWellcome Centre for Integrative Neuroimaging (WIN FMRIB) (L.T.E., F.A.-A., L.G., M.J., S.M.S.), University of Oxford, United Kingdom.
Jiyang JiangCentre for Healthy Brain Ageing, School of Psychiatry (K.A.M., W.W., H.B., J.J., A.T., J.T., P.S.S.), University of New South Wales, Sydney, Australia.
Brian G KralGeneSTAR Research Program (L.R.Y., B.G.K., L.C.B., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.
John B KwokSchool of Medical Sciences (J.B.K., P.R.S.), University of New South Wales, Sydney, Australia.
Leonie LampeDepartment of Neurology, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (L.L., V.A.W.).
David C M LiewaldCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, United Kingdom (M.L., I.J.D., D.C.M.L., M.E.B., J.M.W.).
Pauline MaillardImaging of Dementia and Aging (IDeA) Laboratory, Department of Neurology, University of California-Davis, Davis, CA (P.M.).
Jonathan MarchiniStatistical Genetics and Methods at Regeneron Pharmaceuticals, Inc, New York, NY (J.M.).
Mark E BastinCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, United Kingdom (M.L., I.J.D., D.C.M.L., M.E.B., J.M.W.).
Bernard MazoyerInstitut des Maladies Neurodégénératives, University of Bordeaux, France (B.M.).
Lukas PirpamerClinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Austria (L.P.).
José Rafael RomeroThe Framingham Heart Study, MA (C.L.S., A.S.B., J.R.R., S.S.).
Gennady V RoshchupkinDepartment of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (M.J.K., D.V., N.A., G.V.R., M.W.V., C.M.v.D., M.A.I., H.H.H.A.).
Peter R SchofieldSchool of Medical Sciences (J.B.K., P.R.S.), University of New South Wales, Sydney, Australia.
Matthias L SchroeterLIFE Research Center for Civilization Disease, Leipzig, Germany (M.S.).
David J StottInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom (D.J.S.).
Anbupalam ThalamuthuCentre for Healthy Brain Ageing, School of Psychiatry (K.A.M., W.W., H.B., J.J., A.T., J.T., P.S.S.), University of New South Wales, Sydney, Australia.
Julian TrollorCentre for Healthy Brain Ageing, School of Psychiatry (K.A.M., W.W., H.B., J.J., A.T., J.T., P.S.S.), University of New South Wales, Sydney, Australia.
Christophe TzourioUniversity Bordeaux, Inserm, Bordeaux Population Health Research Center, France (M.S., C.T., S.D.).
Jeroen van der GrondDepartment of Radiology (J.v.d.G.), Leiden University Medical Center, the Netherlands.
Meike W VernooijDepartment of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (M.J.K., D.V., N.A., G.V.R., M.W.V., C.M.v.D., M.A.I., H.H.H.A.).
Veronica A WitteCollaborative Research Center 1052 Obesity Mechanisms, Faculty of Medicine, University of Leipzig, Germany (V.A.W).
Margaret J WrightQueensland Brain Institute (M.J.W.), The University of Queensland, St Lucia, QLD, Australia.
Qiong YangDepartment of Biostatistics, Boston University School of Public Health, Boston, MA (S.L., M.A.L., A.S.B., Q.Y.).
Zoe MorrisNeuroradiology Department, Department of Clinical Neurosciences, Western General Hospital, Edinburgh, United Kingdom (Z.M.).
Siggi SiggurdssonGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX (C.L.S., S.S.).
Bruce PsatyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA (J.B., B.P., W.L.).
Arno VillringerDepartment of Neurology, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (M.L.S., A.V.).
Helena SchmidtGottfried Schatz Research Center (for Cell Signaling, Metabolism and Aging), Medical University of Graz, Austria (P.G.G., H.S.).
Asta K HabergDepartment of Neuromedicine and Movement Science (A.K.H.), Norwegian University of Science and Technology, Trondheim, Norway.
Cornelia M van DuijnDepartment of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (M.J.K., D.V., N.A., G.V.R., M.W.V., C.M.v.D., M.A.I., H.H.H.A.).
J Wouter JukemaDepartment of Cardiology (J.W.J.), Leiden University Medical Center, the Netherlands.
Martin DichgansInstitute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-Universität LMU Munich, Germany (R.M., M.D.).
Ralph L SaccoDepartment of Public Health Sciences, Miller School of Medicine (R.L.S.), University of Miami, FL.
Clinton B WrightNational Institute of Neurological Disorders and Stroke (C.B.W.), National Institutes of Health, Bethesda, MD.
William S KremenCenter for Behavior Genetics of Aging (W.S.K.), University of California, San Diego, La Jolla, CA.
Lewis C BeckerGeneSTAR Research Program (L.R.Y., B.G.K., L.C.B., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.
Paul M ThompsonMark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Marina del Rey (N.J., P.M.T.).
Thomas H MosleyDepartment of Geriatric Medicine, Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson (T.H.M.).
Joanna M WardlawCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, United Kingdom (M.L., I.J.D., D.C.M.L., M.E.B., J.M.W.).
M Arfan IkramDepartment of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (M.J.K., D.V., N.A., G.V.R., M.W.V., C.M.v.D., M.A.I., H.H.H.A.).
Hieab H H AdamsDepartment of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (M.J.K., D.V., N.A., G.V.R., M.W.V., C.M.v.D., M.A.I., H.H.H.A.).
Sudha SeshadriIcelandic Heart Association, Kopavogur (V.G.G., S.S.).
Perminder S SachdevCentre for Healthy Brain Ageing, School of Psychiatry (K.A.M., W.W., H.B., J.J., A.T., J.T., P.S.S.), University of New South Wales, Sydney, Australia.
Stephen M SmithWellcome Centre for Integrative Neuroimaging (WIN FMRIB) (L.T.E., F.A.-A., L.G., M.J., S.M.S.), University of Oxford, United Kingdom.
Lenore LaunerLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program (L.L.), National Institutes of Health, Bethesda, MD.
William LongstrethCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA (J.B., B.P., W.L.).
Charles DeCarliAlzheimer's Disease Center and Imaging of Dementia and Aging (IDeA) Laboratory, Department of Neurology and Center for Neuroscience University of California at Davis (C.D.).
Reinhold SchmidtClinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Austria (E.H., R.S.).
Myriam FornageBrown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, TX (R.X., M.F.).
Stephanie DebetteUniversity Bordeaux, Inserm, Bordeaux Population Health Research Center, France (M.S., C.T., S.D.).
Paul A NyquistGeneSTAR Research Program (L.R.Y., B.G.K., L.C.B., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.
Erasmus MC · NLUNSW Sydney · AUBoston University · USMedical University of Graz · ATInserm · FRJohns Hopkins University · USWellcome Centre for Integrative Neuroimaging · GBLeiden University Medical Center · NLBrown Foundation · USCognitive Research (United States) · USMRC Centre for Regenerative Medicine · GBUniversity Hospital Leipzig · DEUniversity of California San Diego · USUniversity of Iceland · ISUniversity of Southern California · USUniversity of Washington · USAlzheimer Scotland · GBAmerican Medical Informatics Association · USDr. John T. Macdonald Foundation · USGerman Center for Neurodegenerative Diseases · DE

Funding

The VETSA Longitudinal Twin Study of Cognition and Aging (VETSA 4)R01AG050595 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELMAN, JEREMY A, FRANZ, CAROL ELAINE · 2015 to 2024
$28.0M
The VETSA Longitudinal MRI Twin Study of AgingR01AG022381 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KREMEN, WILLIAM S. · 2003 to 2019
$22.3M
TR&D3: Intrinsic Surface MappingP41EB015922 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TOGA, ARTHUR W · 2012 to 2022
$14.1M
Training U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1M
High resolution mapping of the genetic risk for disease in the aging brainR01AG059874 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JAHANSHAD, NEDA · 2018 to 2022
$3.1M
Occult Small Vessel Cerebrovascular Disease in High Risk FamiliesR01NS062059 · NINDS · JOHNS HOPKINS UNIVERSITY · PI NYQUIST, PAUL ALAN · 2009 to 2013
$3.0M
Genetic Markers of Brain AgingZIAAG007270 · NIA · NATIONAL INSTITUTE ON AGING · PI LAUNER, LENORE J · 2009 to 2025
$2.7M
ENIGMA World Aging CenterR56AG058854 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2018 to 2018
$683k
Biotechnology and Biological Sciences Research Council BB/F019394/1Medical Research Council G0700704Medical Research Council G0701120Medical Research Council G1001245Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MR/L023784/2Medical Research Council MR/M013111/1Medical Research Council MR/N027558/1Medical Research Council MR/R024065/1NIA NIH HHS R01 AG022381NIA NIH HHS R01 AG050595NIA NIH HHS R01 AG059874NIA NIH HHS R56 AG058854NIBIB NIH HHS P41 EB015922NIBIB NIH HHS U54 EB020403NINDS NIH HHS R01 NS062059Parkinson's UK J-0901Wellcome Trust
6 · The paper itself

Abstract

background and purposePeriventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings.

methodsParticipants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC.

resultsIn the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 (

conclusionsOur study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.

Indexed as

AgedBrainCerebral Small Vessel DiseasesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedWhite Matterbraingenome-wide association studyneuroimagingrisk factorswhite matter

Identifiers

PMID32517579
PMCPMC7365038
OpenAlexW3034100708

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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.