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Genetic risk factors underlying white matter hyperintensities and cortical atrophy

dc.rights.licenseopenen_US
dc.contributor.authorPATEL, Yash
dc.contributor.authorSHIN, Jean
dc.contributor.authorSLIZ, Eeva
dc.contributor.authorTANG, Ariana
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMISHRA, Aniket
dc.contributor.authorXIA, Rui
dc.contributor.authorHOFER, Edith
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorRAJULA, Hema Sekhar Reddy
dc.contributor.authorWANG, Ruiqi
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBEYER, Frauke
dc.contributor.authorHORN, Katrin
dc.contributor.authorRIEDL, Max
dc.contributor.authorYU, Jing
dc.contributor.authorVÖLZKE, Henry
dc.contributor.authorBÜLOW, Robin
dc.contributor.authorVÖLKER, Uwe
dc.contributor.authorFRENZEL, Stefan
dc.contributor.authorWITTFELD, Katharina
dc.contributor.authorVAN DER AUWERA, Sandra
dc.contributor.authorMOSLEY, Thomas H
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBOUTELOUP, Vincent
dc.contributor.authorLAMBERT, Jean-Charles
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorCHENE, Genevieve
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDUFOUIL, Carole
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTZOURIO, Christophe
dc.contributor.authorMANGIN, Jean-François
dc.contributor.authorGOTTESMAN, Rebecca F
dc.contributor.authorFORNAGE, Myriam
dc.contributor.authorSCHMIDT, Reinhold
dc.contributor.authorYANG, Qiong
dc.contributor.authorWITTE, Veronica
dc.contributor.authorSCHOLZ, Markus
dc.contributor.authorLOEFFLER, Markus
dc.contributor.authorROSHCHUPKIN, Gennady V
dc.contributor.authorIKRAM, M Arfan
dc.contributor.authorGRABE, Hans J
dc.contributor.authorSESHADRI, Sudha
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorPAUS, Tomas
dc.contributor.authorPAUSOVA, Zdenka
dc.date.accessioned2024-11-20T09:09:09Z
dc.date.available2024-11-20T09:09:09Z
dc.date.issued2024-11-04
dc.identifier.issn2041-1723en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/203365
dc.description.abstractEnWhite matter hyperintensities index structural abnormalities in the cerebral white matter, including axonal damage. The latter may promote atrophy of the cerebral cortex, a key feature of dementia. Here, we report a study of 51,065 individuals from 10 cohorts demonstrating that higher white matter hyperintensity volume associates with lower cortical thickness. The meta-GWAS of white matter hyperintensities-associated cortical 'atrophy' identifies 20 genome-wide significant loci, and enrichment in genes specific to vascular cell types, astrocytes, and oligodendrocytes. White matter hyperintensities-associated cortical 'atrophy' showed positive genetic correlations with vascular-risk traits and plasma biomarkers of neurodegeneration, and negative genetic correlations with cognitive functioning. 15 of the 20 loci regulated the expression of 54 genes in the cerebral cortex that, together with their co-expressed genes, were enriched in biological processes of axonal cytoskeleton and intracellular transport. The white matter hyperintensities-cortical thickness associations were most pronounced in cortical regions with higher expression of genes specific to excitatory neurons with long-range axons traversing through the white matter. The meta-GWAS-based polygenic risk score predicts vascular and all-cause dementia in an independent sample of 500,348 individuals. Thus, the genetics of white matter hyperintensities-related cortical atrophy involves vascular and neuronal processes and increases dementia risk.
dc.description.sponsorshipStopping cognitive decline and dementia by fighting covert cerebral small vessel diseaseen_US
dc.description.sponsorshipVaincre les maladies vasculaires cérébrales par un nouveau paradigme de prévention de précision et d'innovation thérapeutiqueen_US
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subject.enHumans
dc.subject.enWhite Matter
dc.subject.enAtrophy
dc.subject.enCerebral Cortex
dc.subject.enGenome-Wide Association Study
dc.subject.enMale
dc.subject.enFemale
dc.subject.enAged
dc.subject.enRisk Factors
dc.subject.enMiddle Aged
dc.subject.enGenetic Predisposition to Disease
dc.subject.enDementia
dc.subject.enMagnetic Resonance Imaging
dc.subject.enCohort Studies
dc.subject.enPolymorphism
dc.subject.enSingle Nucleotide
dc.subject.enAged
dc.subject.en80 and over
dc.title.enGenetic risk factors underlying white matter hyperintensities and cortical atrophy
dc.title.alternativeNat Communen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41467-024-53689-1en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed39496600en_US
bordeaux.journalNature Communicationsen_US
bordeaux.page9517en_US
bordeaux.volume15en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.teamPHARES_BPHen_US
bordeaux.teamHEALTHY_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDNational Heart, Lung, and Blood Instituteen_US
bordeaux.identifier.funderIDFondation Plan Alzheimeren_US
bordeaux.identifier.funderIDFondation Claude Pompidouen_US
bordeaux.identifier.funderIDFondation pour la Recherche Médicaleen_US
bordeaux.identifier.funderIDMutuelle Générale de l'Education Nationaleen_US
bordeaux.identifier.funderIDConseil Régional Aquitaineen_US
bordeaux.import.sourcepubmed
hal.identifierhal-04792507
hal.version1
hal.date.transferred2024-11-20T09:09:17Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
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%20Communications&rft.date=2024-11-04&rft.volume=15&rft.issue=1&rft.spage=9517&rft.epage=9517&rft.eissn=2041-1723&rft.issn=2041-1723&rft.au=PATEL,%20Yash&SHIN,%20Jean&SLIZ,%20Eeva&TANG,%20Ariana&MISHRA,%20Aniket&rft.genre=article


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