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Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease

dc.rights.licenseopenen_US
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDUPERRON, Marie-Gabrielle
dc.contributor.authorKNOL, Maria J.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorLE GRAND, Quentin
dc.contributor.authorEVANS, Tavia E.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMISHRA, Aniket
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTSUCHIDA, Ami
dc.contributor.authorROSHCHUPKIN, Gennady
dc.contributor.authorKONUMA, Takahiro
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTREGOUET, David-Alexandre
dc.contributor.authorROMERO, Jose Rafael
dc.contributor.authorFRENZEL, Stefan
dc.contributor.authorLUCIANO, Michelle
dc.contributor.authorHOFER, Edith
dc.contributor.authorBOURGEY, Mathieu
dc.contributor.authorDUEKER, Nicole D.
dc.contributor.authorDELGADO, Pilar
dc.contributor.authorHILAL, Saima
dc.contributor.authorTANKARD, Rick M.
dc.contributor.authorDUBOST, Florian
dc.contributor.authorSHIN, Jean
dc.contributor.authorSABA, Yasaman
dc.contributor.authorARMSTRONG, Nicola J.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBORDES, Constance
dc.contributor.authorBASTIN, Mark E.
dc.contributor.authorBEISER, Alexa
dc.contributor.authorBRODATY, Henry
dc.contributor.authorBULOW, Robin
dc.contributor.authorCARRERA, Caty
dc.contributor.authorCHEN, Christopher
dc.contributor.authorCHENG, Ching-Yu
dc.contributor.authorDEARY, Ian J.
dc.contributor.authorGAMPAWAR, Piyush G.
dc.contributor.authorHIMALI, Jayandra J.
dc.contributor.authorJIANG, Jiyang
dc.contributor.authorKAWAGUCHI, Takahisa
dc.contributor.authorLI, Shuo
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMACALLI, Melissa
dc.contributor.authorMARQUIS, Pascale
dc.contributor.authorMORRIS, Zoe
dc.contributor.authorMUNOZ MANIEGA, Susana
dc.contributor.authorMIYAMOTO, Susumu
dc.contributor.authorOKAWA, Masakazu
dc.contributor.authorPARADISE, Matthew
dc.contributor.authorPARVA, Pedram
dc.contributor.authorRUNDEK, Tatjana
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSARGURUPREMRAJ, Muralidharan
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSCHILLING, Sabrina
dc.contributor.authorSETOH, Kazuya
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSOUKARIEH, Omar
dc.contributor.authorTABARA, Yasuharu
dc.contributor.authorTEUMER, Alexander
dc.contributor.authorTHALAMUTHU, Anbupalam
dc.contributor.authorTROLLOR, Julian N.
dc.contributor.authorVALDES HERNANDEZ, Maria C.
dc.contributor.authorVERNOOIJ, Meike W.
dc.contributor.authorVOLKER, Uwe
dc.contributor.authorWITTFELD, Katharina
dc.contributor.authorWONG, Tien Yin
dc.contributor.authorWRIGHT, Margaret J.
dc.contributor.authorZHANG, Junyi
dc.contributor.authorZHAO, Wanting
dc.contributor.authorZHU, Yi-Cheng
dc.contributor.authorSCHMIDT, Helena
dc.contributor.authorSACHDEV, Perminder S.
dc.contributor.authorWEN, Wei
dc.contributor.authorYOSHIDA, Kazumichi
dc.contributor.authorJOUTEL, Anne
dc.contributor.authorSATIZABAL, Claudia L.
dc.contributor.authorSACCO, Ralph L.
dc.contributor.authorBOURQUE, Guillaume
dc.contributor.authorLATHROP, Mark
dc.contributor.authorPAUS, Tomas
dc.contributor.authorFERNANDEZ-CADENAS, Israel
dc.contributor.authorYANG, Qiong
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorMAZOYER, Bernard
dc.contributor.authorBOUTINAUD, Philippe
dc.contributor.authorOKADA, Yukinori
dc.contributor.authorGRABE, Hans J.
dc.contributor.authorMATHER, Karen A.
dc.contributor.authorSCHMIDT, Reinhold
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorJOLIOT, Marc
dc.contributor.authorIKRAM, M Arfan
dc.contributor.authorMATSUDA, Fumihiko
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTZOURIO, Christophe
dc.contributor.authorWARDLAW, Joanna M.
dc.contributor.authorSESHADRI, Sudha
dc.contributor.authorADAMS, Hieab H. H.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.date.accessioned2023-05-13T10:23:10Z
dc.date.available2023-05-13T10:23:10Z
dc.date.issued2023-04-17
dc.identifier.issn1546-170X (Electronic) 1078-8956 (Print)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182095
dc.description.abstractEnPerivascular 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.
dc.description.sponsorshipEtude de cohorte sur la santé des étudiants - ANR-10-COHO-0005en_US
dc.description.sponsorshipStopping cognitive decline and dementia by fighting covert cerebral small vessel diseaseen_US
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enGenomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease
dc.title.alternativeNat Meden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41591-023-02268-wen_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed37069360en_US
dc.description.sponsorshipEuropeStudy on Environmental and GenomeWide predictors of early structural brain Alterations in Young studentsen_US
bordeaux.journalNature Medicineen_US
bordeaux.page950-962en_US
bordeaux.volume29en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue4en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.institutionCNRS
bordeaux.teamHEALTHY_BPHen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-04096692
hal.version1
hal.date.transferred2023-05-13T10:23:37Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature%20Medicine&rft.date=2023-04-17&rft.volume=29&rft.issue=4&rft.spage=950-962&rft.epage=950-962&rft.eissn=1546-170X%20(Electronic)%201078-8956%20(Print)&rft.issn=1546-170X%20(Electronic)%201078-8956%20(Print)&rft.au=DUPERRON,%20Marie-Gabrielle&KNOL,%20Maria%20J.&LE%20GRAND,%20Quentin&EVANS,%20Tavia%20E.&MISHRA,%20Aniket&rft.genre=article


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