ArticleNature medicine2023
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease.
Open access · hybridAbstract read
In one paragraph
Article in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
16.5field-weighted citation impact, top 1% of its field
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.
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.
Who cites it
68 citing papers in PubMed, 112 citations in OpenAlex.
- Outdoor Air Pollution, Perivascular Space Morphology, and Cognition in Preadolescence.Biological psychiatry global open science · 2026Article
- Perivascular Spaces as Determinants of Amyloid, Tau, and Vascular Biomarker Progression.Annals of neurology · 2026Article
- Genetic Insights Into Protective Effects of GLP-1 Receptor Agonists on Stroke and Alzheimer Disease Across Ancestries.Neurology. Genetics · 2026Article
- Article
- Article
- Fibronectin mediates APOE4-driven blood-brain barrier dysfunction in Alzheimer's disease.Nature aging · 2026Article
- Human genetics across levels of biological organization.Nature reviews. Genetics · 2026Review
- 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 · 2026Review
- Glycocalyx and basal lamina in neurological disorders.Matrix biology : journal of the International Society for Matrix Biology · 2026Review
- UK Biobank at 20 - a growing, global resource for dementia research.Nature reviews. Neurology · 2026Review
- Leveraging Mendelian randomization to inform drug discovery and development for ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Genetic Architecture of Perivascular Space Morphology in the Pediatric Brain.bioRxiv : the preprint server for biology · 2026Article
- Ultra-rare variants in LAMA2 are risk factors for frontotemporal dementia and motor neuron disease.Human molecular genetics · 2026Article
- Multiomics Profiling Supports Cathepsin B as a Protective Factor in Cerebral Small Vessel Disease.Research square · 2026Article
- Impact of enlarged perivascular spaces on endovascular therapy outcomes in patients with large ischaemic core: A post-hoc analysis of the ANGEL-ASPECT trial.Journal of translational internal medicine · 2026Article
- Genetically Simulated GLP-1 Receptor Agonism and Cerebral Small Vessel Disease.Neurology. Genetics · 2026Article
- Article
- Endothelial TRIM47 regulates blood-brain barrier integrity and cognition via the KEAP1/NRF2 signalling pathway in mice.Communications biology · 2026Article
- Genetically Predicted Levels of Lipoprotein(a) and Risk of Cerebrovascular Disease.Journal of the American Heart Association · 2026Article
- Causal Effect of Dietary Patterns on Cerebral Small Vessel Disease: A Mendelian Randomization Study.Food science & nutrition · 2026Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
89 authors at 20 institutions in 13 countries.
Marie-Gabrielle Duperron *Bordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.ORCID http://orcid.org/0000-0001-7408-7792
Maria J Knol *Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0002-3597-1531
Quentin Le Grand *Bordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.ORCID http://orcid.org/0000-0002-9299-0747
Tavia E Evans *Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0003-2390-286X
Aniket Mishra *Bordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.
Ami Tsuchida *Bordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.ORCID http://orcid.org/0000-0001-5160-6203
Gennady RoshchupkinDepartment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0002-3403-2313
Takahiro KonumaDepartment of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
David-Alexandre TrégouëtBordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.
Jose Rafael RomeroDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1101-2950
Stefan FrenzelDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Michelle LucianoSchool of Psychology, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-7306-3008
Edith HoferClinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.
Mathieu BourgeyDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-8432-834X
Nicole D DuekerJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
Pilar DelgadoInstitut de Recerca Vall d'hebron, Neurovascular Research Lab, Universitat Autònoma de Barcelona, Barcelona, Spain.
Saima HilalMemory Aging and Cognition Center, National University Health System, Singapore, Singapore.
Rick M TankardDepartment of Mathematics and Statistics, Curtin University, Perth, Western Australia, Australia.ORCID http://orcid.org/0000-0002-8847-9401
Florian DubostDepartment of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Jean ShinThe Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0001-7353-5178
Yasaman SabaBordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.ORCID http://orcid.org/0000-0002-3549-2493
Nicola J ArmstrongDepartment of Mathematics and Statistics, Curtin University, Perth, Western Australia, Australia.ORCID http://orcid.org/0000-0002-4477-293X
Constance BordesBordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.ORCID http://orcid.org/0000-0003-3367-1778
Mark E BastinCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Alexa BeiserDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.
Henry BrodatyCentre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry & Mental Health, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0001-9487-6617
Robin BülowInstitute for Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0003-1884-5784
Caty CarreraStroke Pharmacogenomics and Genetics Group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Christopher ChenMemory Aging and Cognition Center, National University Health System, Singapore, Singapore.
Ching-Yu ChengSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.ORCID http://orcid.org/0000-0003-0655-885X
Ian J DearySchool of Psychology, University of Edinburgh, Edinburgh, UK.
Piyush G GampawarInstitute for Molecular Biology & Biochemistry, Gottfried Schatz Research Center (for Cell Signaling, Metabolism and Aging), Medical University of Graz, Graz, Austria.
Jayandra J HimaliDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1391-9481
Jiyang JiangCentre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry & Mental Health, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-2147-6302
Takahisa KawaguchiCenter for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Shuo LiThe Framingham Heart Study, Framingham, MA, USA.ORCID http://orcid.org/0000-0003-2331-2448
Melissa MacalliBordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.ORCID http://orcid.org/0000-0003-3008-8720
Pascale MarquisDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Zoe MorrisNeuroimaging, Department of Clinical Neurosciences, Royal Infirmary of Edinburgh, Edinburgh, UK.
Susana Muñoz ManiegaCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0001-5185-6384
Susumu MiyamotoKyoto University Hospital, Kyoto, Japan.
Masakazu OkawaDepartment of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID http://orcid.org/0000-0002-5414-1293
Matthew ParadiseCentre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry & Mental Health, University of New South Wales, Sydney, New South Wales, Australia.
Pedram ParvaThe Framingham Heart Study, Framingham, MA, USA.
Tatjana RundekDepartment of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.ORCID http://orcid.org/0000-0002-7115-9815
Muralidharan SargurupremrajBordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.
Sabrina SchillingBordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.
Kazuya SetohCenter for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Omar SoukariehBordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.
Yasuharu TabaraCenter for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-8309-094X
Anbupalam ThalamuthuCentre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry & Mental Health, University of New South Wales, Sydney, New South Wales, Australia.
Julian N TrollorCentre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry & Mental Health, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-7685-2977
Maria C Valdés HernándezCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Meike W VernooijDepartment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Uwe VölkerInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
Katharina WittfeldDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0003-4383-5043
Tien Yin WongSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Margaret J WrightQueensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0001-7133-4970
Junyi ZhangDepartment of Neurology, Peking Union Medical College Hospital, Beijing, China.
Wanting ZhaoSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Yi-Cheng ZhuDepartment of Neurology, Peking Union Medical College Hospital, Beijing, China.
Helena SchmidtInstitute for Molecular Biology & Biochemistry, Gottfried Schatz Research Center (for Cell Signaling, Metabolism and Aging), Medical University of Graz, Graz, Austria.ORCID http://orcid.org/0000-0001-9773-9992
Perminder S SachdevCentre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry & Mental Health, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-9595-3220
Wei WenCentre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry & Mental Health, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-2753-3870
Kazumichi YoshidaDepartment of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Anne JoutelInstitut de Psychiatrie et Neurosciences de Paris, Université Paris Cité, Inserm, France.
Claudia L SatizabalDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.
Ralph L SaccoDepartment of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.
Guillaume BourqueDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-3933-9656
CHARGE consortium
Mark LathropDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Tomas PausUniversity of Montreal, Faculty of Medicine, Departments of Psychiatry and Neuroscience, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0003-1495-9338
Israel Fernandez-CadenasStroke Pharmacogenomics and Genetics Group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Qiong YangThe Framingham Heart Study, Framingham, MA, USA.
Bernard MazoyerGroupe d'Imagerie Neurofonctionelle - Institut des maladies neurodégénératives (GIN-IMN), UMR 5293, University of Bordeaux, CNRS, CEA, Bordeaux, France.ORCID http://orcid.org/0000-0003-0970-2837
Philippe BoutinaudFealinx, Lyon, France.
Yukinori OkadaDepartment of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.ORCID http://orcid.org/0000-0002-0311-8472
Hans J GrabeDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0003-3684-4208
Karen A MatherCentre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry & Mental Health, University of New South Wales, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-4143-8941
Reinhold SchmidtClinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.
Marc JoliotGroupe d'Imagerie Neurofonctionelle - Institut des maladies neurodégénératives (GIN-IMN), UMR 5293, University of Bordeaux, CNRS, CEA, Bordeaux, France.ORCID http://orcid.org/0000-0001-7792-308X
M Arfan IkramDepartment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0003-0372-8585
Fumihiko MatsudaCenter for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Christophe TzourioBordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.
Joanna M WardlawCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-9812-6642
Sudha SeshadriDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6135-2622
Hieab H H AdamsDepartment of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands. h.adams@erasmusmc.nl.ORCID http://orcid.org/0000-0003-3687-2508
Stéphanie DebetteBordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France. stephanie.debette@u-bordeaux.fr.ORCID http://orcid.org/0000-0001-8675-7968
Université de Bordeaux · FRBoston University · USUNSW Sydney · AUErasmus MC · NLKyoto University · JPUniversitätsmedizin Greifswald · DEMcGill University · CAMedical University of Graz · ATUniversity of Edinburgh · GBCentre National de la Recherche Scientifique · FRNational University of Singapore · SGUniversity of Miami · USChinese Academy of Medical Sciences & Peking Union Medical College · CNCurtin University · AUHospital de Sant Pau · ESSingapore National Eye Center · SGUK Dementia Research Institute · GBUniversity of Toronto · CAAdolfo Ibáñez University · CLEdinburgh Royal Infirmary · GB
Funding
FRAMINGHAM HEART STUDY - YEAR 5 EXAM75N92019D00031 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI RAMACHANDRAN, VASAN · 2019 to 2024
$29.8MPRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9MSTROKE INCIDENCE AND RISK FACTORS IN A TRI-ETHNIC REGIONR01NS029993 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ELKIND, MITCHELL S, SACCO, RALPH L. · 1993 to 2019
$19.2MTemporal 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
$12.3MStroke Incidence and Risk Factors in a Tri-Ethnic RegionR37NS029993 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ELKIND, MITCHELL S, SACCO, RALPH L. · 2008 to 2014
$12.1MCognitively Healthy Nonagenarians in the Cross Cohort Collaboration (CCC)RF1AG059421 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SESHADRI, SUDHA · 2018 to 2018
$6.1MPreclinical AD: Correlates of Amyloid, Tau PET and fcMRI in Framingham Gen 3 Young AdultsR01AG049607 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SESHADRI, SUDHA · 2015 to 2019
$3.1MMechanisms of Aging in C. elegansR01AG025941 · NIA · STANFORD UNIVERSITY · PI DAVIS, RONALD WAYNE · 2007 to 2017
$3.1MEnlarged Perivascular Spaces as Markers of Vascular and Alzheimer pathology: predictors, pathophysiology and clinical consequencesR01AG059725 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI ROMERO, JOSE RAFAEL · 2019 to 2023
$3.1MCHARGE: Identifying Risk & Protective SNV for AD in ADSP Case-control SampleU01AG049505 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SESHADRI, SUDHA · 2014 to 2017
$3.0MADSP Follow-up in Multi-Ethnic Cohorts via Endophenotypes, Omics & Model SystemsU01AG052409 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI FORNAGE, MYRIAM, SESHADRI, SUDHA · 2016 to 2020
$1.6MNeurotrophic Factors: Genetic Variation and Serum Levels in Brain AgingR01AG031287 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SESHADRI, SUDHA · 2009 to 2010
$1.2MBiotechnology and Biological Sciences Research Council BB/F019394/1Medical Research Council MR/J006971/1Medical Research Council MR/K026992/1NHLBI NIH HHS 75N92019D00031NHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS N01 HC025195NHLBI NIH HHS N02 HL064278NIA NIH HHS R01 AG025941NIA NIH HHS R01 AG031287NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG054076NIA NIH HHS R01 AG059725NIA NIH HHS RF1 AG059421NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG052409NINDS NIH HHS R01 NS017950NINDS NIH HHS R01 NS029993NINDS NIH HHS R37 NS029993NINDS NIH HHS R56 NS029993The Dunhill Medical Trust R380R/1114
Abstract
Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.
Indexed as
Cerebral Small Vessel DiseasesStrokeEndothelial CellsGenome-Wide Association StudyGenomicsHumansMagnetic Resonance Imaging
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
None linked
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.