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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]
hal.structure.identifierDeutsches Zentrum für Neurodegenerative Erkrankungen [Ulm] [DZNE]
dc.contributor.authorLE GRAND, Quentin
hal.structure.identifierBordeaux population health [BPH]
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorTSUCHIDA, Ami
hal.structure.identifierDeutsches Zentrum für Neurodegenerative Erkrankungen [Ulm] [DZNE]
dc.contributor.authorKOCH, Alexandra
hal.structure.identifierDeutsches Zentrum für Neurodegenerative Erkrankungen [Ulm] [DZNE]
dc.contributor.authorIMTIAZ, Mohammed-Aslam
hal.structure.identifierDeutsches Zentrum für Neurodegenerative Erkrankungen [Ulm] [DZNE]
dc.contributor.authorAZIZ, N. Ahmad
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorVIGNERON, Chloé
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
hal.structure.identifierGroupe d'imagerie neurofonctionnelle [GIN]
dc.contributor.authorZAGO, Laure
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorLATHROP, Mark
hal.structure.identifierCentre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada]
hal.structure.identifierUniversité de Montréal [UdeM]
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
hal.structure.identifierImperial College London
dc.contributor.authorMATTHEWS, Paul
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMISHRA, Aniket
hal.structure.identifierBordeaux population health [BPH]
hal.structure.identifierUniversität Bonn = University of Bonn
dc.contributor.authorBRETELER, Monique
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTZOURIO, Christophe
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stéphanie
dc.date.accessioned2025-01-14T09:30:12Z
dc.date.available2025-01-14T09:30:12Z
dc.date.issued2024-05-29
dc.identifier.issn1359-4184en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/204255
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.sponsorshipUniversity of Bordeaux Graduate School in Digital Public Health - ANR-17-EURE-0019en_US
dc.language.isoENen_US
dc.title.enDiffusion imaging genomics provides novel insight into early mechanisms of cerebral small vessel disease
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41380-024-02604-7en_US
dc.subject.halSciences du Vivant [q-bio]/Génétique/Génétique humaineen_US
dc.identifier.pubmed38811690en_US
bordeaux.journalMolecular Psychiatryen_US
bordeaux.volume2024en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires (BMC) - UMR 1034en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-04600033
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
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