Evidence map›Paper›PMID 33293549›Full record

SynthesisNature communications2020

Cerebral small vessel disease genomics and its implications across the lifespan.

Muralidharan Sargurupremraj, Hideaki Suzuki, Xueqiu Jian, Chloé Sarnowski, Tavia E Evans, Joshua C Bis, Gudny Eiriksdottir, Saori Sakaue, Natalie Terzikhan, Mohamad Habes and 108 more

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

Synthesis in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed, 9 pooled it
7.8field-weighted citation impact, top 2% 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

125 citing papers in PubMed, 9 syntheses or guidelines pooled it, 201 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. A genome-wide association meta-analysis of all-cause and vascular dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Trial
  11. Article
  12. Cognition in Cardiovascular Disease.Current neurology and neuroscience reports · 2026
    Review
  13. Article
  14. Article
  15. Effects of BACE2 polymorphisms on verbal memory in the general population.European archives of psychiatry and clinical neuroscience · 2026
    Article
  16. Article
  17. Genetic analysis of imaging-derived phenotypes.Nature reviews. Genetics · 2026
    Review
  18. Article
  19. Glycocalyx and basal lamina in neurological disorders.Matrix biology : journal of the International Society for Matrix Biology · 2026
    Review
  20. 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

65 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

118 authors at 20 institutions in 17 countries.

Muralidharan SargurupremrajUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, 33000, Bordeaux, France.
Hideaki SuzukiTohoku Medical Megabank Organization, Tohoku University, 2-1, Seiryo, Aoba, Sendai, 980-8573, Japan.
Xueqiu JianUniversity of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, 77030, USA.ORCID 0000-0002-0313-6494
Chloé SarnowskiDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.ORCID 0000-0002-6090-7099
Tavia E EvansDepartment of Clinical Genetics, Erasmus MC, 3015 GE, Rotterdam, The Netherlands.
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98101, USA.
Gudny EiriksdottirIcelandic Heart Association, IS-201, Kópavogur, Iceland.
Saori SakaueDepartment of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.ORCID 0000-0003-3618-9717
Natalie TerzikhanDepartment of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, The Netherlands.
Mohamad HabesGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, 78229, USA.
Wei ZhaoDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109-2029, USA.ORCID 0000-0001-7388-0692
Nicola J ArmstrongMathematics and Statistics, Murdoch University, Murdoch, WA, 6150, Australia.
Edith HoferClinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, 8036, Graz, Austria.
Lisa R YanekGeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.ORCID 0000-0001-7117-1075
Saskia P HagenaarsCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
Rajan B KumarDepartment of Public Health Sciences, University of California at Davis, Davis, CA, 95616, USA.
Erik B van den AkkerSection of Molecular Epidemiology, Biomedical Sciences, Leiden university Medical Center, 2333 ZA, Leiden, The Netherlands.
Rebekah E McWhirterCentre for Law and Genetics, Faculty of Law, University of Tasmania, Hobart, TAS, 7005, Australia.ORCID 0000-0002-9409-8074
Stella TrompetDepartment of Internal Medicine, section of gerontology and geriatrics, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
Aniket MishraUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, 33000, Bordeaux, France.ORCID 0000-0002-8141-1543
Yasaman SabaUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, 33000, Bordeaux, France.
Claudia L SatizabalGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, 78229, USA.ORCID 0000-0002-1115-4430
Gregory BeaudetUniversity of Bordeaux, IMN, UMR 5293, 33000, Bordeaux, France.
Laurent PetitUniversity of Bordeaux, IMN, UMR 5293, 33000, Bordeaux, France.
Ami TsuchidaUniversity of Bordeaux, IMN, UMR 5293, 33000, Bordeaux, France.ORCID 0000-0001-5160-6203
Laure ZagoUniversity of Bordeaux, IMN, UMR 5293, 33000, Bordeaux, France.ORCID 0000-0001-8235-2154
Sabrina SchillingUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, 33000, Bordeaux, France.
Sigurdur SigurdssonIcelandic Heart Association, IS-201, Kópavogur, Iceland.
Rebecca F GottesmanJohns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Cora E LewisUniversity of Alabama at Birmingham School of Medicine, Birmingham, AL, 35233, USA.
Neelum T AggarwalDepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL, 60612, USA.
Oscar L LopezDepartments of Neurology and Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109-2029, USA.ORCID 0000-0002-3575-5468
Maria C Valdés HernándezCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
Jeroen van der GrondDepartment of Radiology, Leiden University medical Center, 2333 ZA, Leiden, The Netherlands.
Margaret J WrightQueensland Brain Institute, The University of Queensland, St Lucia, QLD, 4072, Australia.ORCID 0000-0001-7133-4970
Maria J KnolDepartment of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, The Netherlands.ORCID 0000-0002-3597-1531
Marcus DörrDepartment of Internal Medicine B, University Medicine Greifswald, 17475, Greifswald, Germany.
Russell J ThomsonMenzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 7000, Australia.
Constance BordesUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, 33000, Bordeaux, France.
Quentin Le GrandUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, 33000, Bordeaux, France.ORCID 0000-0002-9299-0747
Marie-Gabrielle DuperronUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, 33000, Bordeaux, France.
Albert V SmithIcelandic Heart Association, IS-201, Kópavogur, Iceland.ORCID 0000-0003-1942-5845
David S KnopmanMayo Clinic, Rochester, MN, 55905, USA.
Pamela J SchreinerUniversity of Minnesota School of Public Health, Minneapolis, MN, 55455, USA.
Denis A EvansDepartment of Internal Medicine, Rush University Medical Center, Chicago, IL, 60612, USA.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Pediatrics at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.ORCID 0000-0001-7191-1723
Alexa S BeiserDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
Susana Muñoz ManiegaCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
Marian BeekmanSection of Molecular Epidemiology, Biomedical Sciences, Leiden university Medical Center, 2333 ZA, Leiden, The Netherlands.ORCID 0000-0003-0585-6206
Julian TrollorCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, 2052, Australia.ORCID 0000-0002-7685-2977
David J StottInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
Meike W VernooijDepartment of Radiology & Nuclear Medicine, Erasmus MC, 3015 GE, Rotterdam, The Netherlands.
Katharina WittfeldGerman Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, 17489, Greifswald, Germany.ORCID 0000-0003-4383-5043
Wiro J NiessenDepartment of Radiology & Nuclear Medicine, Erasmus MC, 3015 GE, Rotterdam, The Netherlands.
Aicha SoumaréUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, 33000, Bordeaux, France.ORCID 0000-0002-0178-6506
Eric BoerwinkleUniversity of Texas Health Science Center at Houston School of Public Health, Houston, TX, 77030, USA.
Stephen SidneyKaiser Permanente Division of Research, Oakland, CA, 94612, USA.
Stephen T TurnerDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, 55905, USA.
Gail DaviesInstitute for Medical Informatics, Statistics and Documentation, Medical University of Graz, 8036, Graz, Austria.
Anbupalam ThalamuthuInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Pediatrics at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
Uwe VölkerInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475, Greifswald, Germany.ORCID 0000-0002-5689-3448
Mark A van BuchemRow Fogo Centre for Ageing and The Brain, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
R Nick BryanThe University of Texas at Austin Dell Medical School, Austin, TX, 78712, USA.
Josée DupuisGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, 78229, USA.ORCID 0000-0003-2871-3603
Mark E BastinInstitute for Medical Informatics, Statistics and Documentation, Medical University of Graz, 8036, Graz, Austria.
David AmesNational Ageing Research Institute Royal Melbourne Hospital, Parkville, VIC, 3052, Australia.
Alexander TeumerDepartment of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, The Netherlands.ORCID 0000-0002-8309-094X
Philippe AmouyelInserm U1167, 59000, Lille, France.ORCID 0000-0001-9088-234X
John B KwokBrain and Mind Centre - The University of Sydney, Camperdown, NSW, 2050, Australia.
Robin BülowDepartment of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, 17489, Greifswald, Germany.
Ian J DearyInstitute for Medical Informatics, Statistics and Documentation, Medical University of Graz, 8036, Graz, Austria.
Peter R SchofieldSchool of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.ORCID 0000-0003-2967-9662
Henry BrodatyInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Pediatrics at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.ORCID 0000-0001-9487-6617
Jiyang JiangInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Pediatrics at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.ORCID 0000-0002-2147-6302
Yasuharu TabaraCenter for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.
Kazuya SetohDepartment of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.
Susumu MiyamotoDepartment of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.
Kazumichi YoshidaDepartment of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.
Manabu NagataDepartment of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.
Yoichiro KamataniLaboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan.ORCID 0000-0001-8748-5597
Fumihiko MatsudaCenter for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.
Bruce M PsatyDepartments of Epidemiology, Medicine and Health Services, University of Washington, Seattle, WA, 98195, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
Philip L De JagerCenter for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, 10032, USA.ORCID 0000-0002-8057-2505
Thomas H MosleyMemory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Perminder S SachdevInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Pediatrics at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.ORCID 0000-0002-9595-3220
Reinhold SchmidtDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109-2029, USA.
Helen R WarrenWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 4NS, UK.ORCID 0000-0003-0511-1386
Evangelos EvangelouDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, SW7 2AZ, UK.ORCID 0000-0002-5488-2999
David-Alexandre TrégouëtUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, 33000, Bordeaux, France.
International Network against Thrombosis (INVENT) Consortium
International Headache Genomics Consortium (IHGC)
Mohammad A IkramDepartment of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, The Netherlands.ORCID 0000-0003-0372-8585
Wei WenCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, 2052, Australia.ORCID 0000-0003-2753-3870
Charles DeCarliDepartment of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA, 95817, USA.
Velandai K SrikanthMenzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 7000, Australia.
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.ORCID 0000-0002-3246-8359
Eline P SlagboomSection of Molecular Epidemiology, Biomedical Sciences, Leiden university Medical Center, 2333 ZA, Leiden, The Netherlands.ORCID 0000-0002-2875-4723
Sharon L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109-2029, USA.
Yukinori OkadaDepartment of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.ORCID 0000-0002-0311-8472
Bernard MazoyerUniversity of Bordeaux, IMN, UMR 5293, 33000, Bordeaux, France.ORCID 0000-0003-0970-2837
Joanna M WardlawCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.ORCID 0000-0002-9812-6642
Paul A NyquistDepartment of Neurology, Johns Hopkins School of Medicine, Baltimone, MD, 21205, USA.
Karen A MatherCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, 2052, Australia.
Hans J GrabeDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475, Greifswald, Germany.ORCID 0000-0003-3684-4208
Helena SchmidtGottfried Schatz Research Center, Department of Molecular Biology and Biochemistry, Medical University of Graz, 8010, Graz, Austria.
Cornelia M Van DuijnNuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.ORCID 0000-0002-2374-9204
Vilmundur GudnasonIcelandic Heart Association, IS-201, Kópavogur, Iceland.ORCID 0000-0001-5696-0084
William T LongstrethDepartments of Neurology and Epidemiology, University of Washington, Seattle, WA, 98104-2420, USA.
Lenore J LaunerLaboratory of Epidemiology, Demography, and Biometry, National Institute of Aging, The National Institutes of Health, Bethesda, MD, 20892, USA.
Mark LathropUniversity of McGill Genome Center, Montreal, QC, H3A 0G1, Canada.
Sudha SeshadriGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, 78229, USA.
Christophe TzourioUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, 33000, Bordeaux, France.
Hieab H AdamsDepartment of Clinical Genetics, Erasmus MC, 3015 GE, Rotterdam, The Netherlands.ORCID 0000-0003-3687-2508
Paul M MatthewsDepartment of Brain Sciences, Imperial College London, London, W12 0NN, UK.ORCID 0000-0002-1619-8328
Myriam FornageUniversity of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, 77030, USA. myriam.fornage@uth.tmc.edu.ORCID 0000-0003-0677-8158
Stéphanie DebetteUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, 33000, Bordeaux, France. stephanie.debette@u-bordeaux.fr.ORCID 0000-0001-8675-7968
Université de Bordeaux · FRBroad Institute · USLeiden University Medical Center · NLErasmus MC · NLUniversity of Helsinki · FIBrigham and Women's Hospital · USInserm · FRKyoto University · JPThe Lundquist Institute · USUniversity of Tartu · EEBoston University · USLeiden University · NLMedical University of Graz · ATOslo University Hospital · NOUniversitätsmedizin Greifswald · DEUniversity of Copenhagen · DKUniversity of Minnesota · USdeCODE Genetics (Iceland) · ISHelsinki University Hospital · FIKing's College London · GB

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
THE FRAMINGHAM HEART STUDYN01HC25195 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI RAMACHANDRAN, VASAN S · 2007 to 2014
$83.8M
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
ZINC AND CA EDTA THERAPY OF PLUMBISMM01RR000052 · NCRR · JOHNS HOPKINS UNIVERSITY · PI VINING, EILEEN PATRICE · 1985 to 2007
$37.3M
FRAMINGHAM HEART STUDY - YEAR 5 EXAM75N92019D00031 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · 2019 to 2024
$29.8M
UC Davis Alzheimer's Disease Core CenterP30AG010129 · NIA · UNIVERSITY OF CALIFORNIA DAVIS · PI JOHNSON, DAVID K · 1991 to 2020
$28.3M
Building on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6M
South Texas Alzheimer's Disease Research CenterP30AG066546 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Sudha Seshadri · 2021 to 2026
$24.0M
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
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Biotechnology and Biological Sciences Research Council BB/F019394/1Department of HealthIntramural NIH HHS Z01 HL004607Medical Research Council G0700704Medical Research Council G0701120Medical Research Council G0900897Medical Research Council G1001245Medical Research Council G9409531Medical Research Council G9409634Medical Research Council G9901399Medical Research Council MC_PC_17114Medical Research Council MR/K026992/1Medical Research Council MR/K501013/1Medical Research Council MR/M013111/1Medical Research Council MR/N026934/1Medical Research Council MR/N027558/1Medical Research Council MR/R024065/1Medical Research Council MR/S015132/1NCRR NIH HHS M01 RR000052NCRR NIH HHS UL1 RR025005NHGRI NIH HHS U01 HG004446NHGRI NIH HHS U01 HG004729NHLBI NIH HHS 75N92019D00031NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS HHSN268201700001INHLBI NIH HHS HHSN268201700002INHLBI NIH HHS HHSN268201700003INHLBI NIH HHS HHSN268201700004INHLBI NIH HHS HHSN268201700005INHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS HHSN268201800003INHLBI NIH HHS HHSN268201800004INHLBI NIH HHS HHSN268201800005INHLBI NIH HHS HHSN268201800006INHLBI NIH HHS HHSN268201800007INHLBI NIH HHS N01HC25195NHLBI NIH HHS N01HC55222NHLBI NIH HHS N01HC65226NHLBI NIH HHS N01HC85079NHLBI NIH HHS N01HC85080NHLBI NIH HHS N01HC85081NHLBI NIH HHS N01HC85082NHLBI NIH HHS N01HC85083NHLBI NIH HHS N01HC85086NHLBI NIH HHS N02 HL64278NHLBI NIH HHS R01 HL085251NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL120393NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL130114NIA NIH HHS N01AG12100NIA NIH HHS P30 AG010129NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG066546NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG033040NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG054076NIA NIH HHS RF1 AG059421NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG052409NIA NIH HHS U01 AG058589NINDS NIH HHS R01 NS017950NINDS NIH HHS R01 NS062059NINDS NIH HHS R01 NS087541NINDS NIH HHS UH2 NS100605
6 · The paper itself

Abstract

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.

Indexed as

AdultAgedAged, 80 and overAlzheimer DiseaseCerebral Small Vessel DiseasesDiffusion Tensor ImagingFemaleGenetic LociGenome-Wide Association StudyHumansHypertensionMaleMedical History TakingMendelian Randomization AnalysisMiddle AgedRisk Assessment

Identifiers

PMID33293549
PMCPMC7722866
OpenAlexW3094435518

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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.