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Diffusion imaging genomics provides novel insight into early mechanisms of cerebral small vessel disease

dc.rights.licenseopenen_US
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorLE GRAND, Quentin
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTSUCHIDA, Ami
dc.contributor.authorKOCH, Alexandra
dc.contributor.authorIMTIAZ, Mohammed-Aslam
dc.contributor.authorAZIZ, N Ahmad
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorVIGNERON, Chloe
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorZAGO, Laure
dc.contributor.authorLATHROP, Mark
dc.contributor.authorDUBRAC, Alexandre
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorCOUFFINHAL, Thierry
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorCRIVELLO, Fabrice
dc.contributor.authorMATTHEWS, Paul M
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMISHRA, Aniket
dc.contributor.authorBRETELER, Monique M B
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTZOURIO, Christophe
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.date.accessioned2024-06-27T12:05:54Z
dc.date.available2024-06-27T12:05:54Z
dc.date.issued2024-05-29
dc.identifier.issn1814-1412en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/200673
dc.description.abstractEnCerebral small vessel disease (cSVD) is a leading cause of stroke and dementia. Genetic risk loci for white matter hyperintensities (WMH), the most common MRI-marker of cSVD in older age, were recently shown to be significantly associated with white matter (WM) microstructure on diffusion tensor imaging (signal-based) in young adults. To provide new insights into these early changes in WM microstructure and their relation with cSVD, we sought to explore the genetic underpinnings of cutting-edge tissue-based diffusion imaging markers across the adult lifespan. We conducted a genome-wide association study of neurite orientation dispersion and density imaging (NODDI) markers in young adults (i-Share study: N = 1 758, (mean[range]) 22.1[18-35] years), with follow-up in young middle-aged (Rhineland Study: N = 714, 35.2[30-40] years) and late middle-aged to older individuals (UK Biobank: N = 33 224, 64.3[45-82] years). We identified 21 loci associated with NODDI markers across brain regions in young adults. The most robust association, replicated in both follow-up cohorts, was with Neurite Density Index (NDI) at chr5q14.3, a known WMH locus in VCAN. Two additional loci were replicated in UK Biobank, at chr17q21.2 with NDI, and chr19q13.12 with Orientation Dispersion Index (ODI). Transcriptome-wide association studies showed associations of STAT3 expression in arterial and adipose tissue (chr17q21.2) with NDI, and of several genes at chr19q13.12 with ODI. Genetic susceptibility to larger WMH volume, but not to vascular risk factors, was significantly associated with decreased NDI in young adults, especially in regions known to harbor WMH in older age. Individually, seven of 25 known WMH risk loci were associated with NDI in young adults. In conclusion, we identified multiple novel genetic risk loci associated with NODDI markers, particularly NDI, in early adulthood. These point to possible early-life mechanisms underlying cSVD and to processes involving remyelination, neurodevelopment and neurodegeneration, with a potential for novel approaches to prevention.
dc.description.sponsorshipEtude de cohorte sur la santé des étudiantsen_US
dc.description.sponsorshipIdEx Bordeauxen_US
dc.description.sponsorshipStopping cognitive decline and dementia by fighting covert cerebral small vessel disease - ANR-18-RHUS-0002en_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 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enDiffusion imaging genomics provides novel insight into early mechanisms of cerebral small vessel disease
dc.title.alternativeMol Psychiatryen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41380-024-02604-7en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed38811690en_US
dc.description.sponsorshipEuropeNeurodegenerative Disease Research (JPND)en_US
bordeaux.journalMolecular Psychiatryen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_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
bordeaux.identifier.funderIDHorizon 2020en_US
bordeaux.identifier.funderIDFondation Philippe Chatrieren_US
bordeaux.identifier.funderIDFondation pour la Recherche Médicaleen_US
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Molecular%20Psychiatry&rft.date=2024-05-29&rft.eissn=1814-1412&rft.issn=1814-1412&rft.au=LE%20GRAND,%20Quentin&TSUCHIDA,%20Ami&KOCH,%20Alexandra&IMTIAZ,%20Mohammed-Aslam&AZIZ,%20N%20Ahmad&rft.genre=article


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