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Genomic studies across the lifespan point to early mechanisms determining subcortical volumes

dc.rights.licenseopenen_US
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorLE GRAND, Quentin
dc.contributor.authorSATIZABAL, Claudia L.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSARGURUPREMRAJ, Muralidharan
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMISHRA, Aniket
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSOUMARE, Aicha
dc.contributor.authorLAURENT, Alexandre
dc.contributor.authorCRIVELLO, Fabrice
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorTSUCHIDA, Ami
dc.contributor.authorSHIN, Jean
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMACALLI, Melissa
dc.contributor.authorSINGH, Baljeet
dc.contributor.authorBEISER, Alexa S.
dc.contributor.authorDECARLI, Charles
dc.contributor.authorFLETCHER, Evan
dc.contributor.authorPAUS, Tomas
dc.contributor.authorLATHROP, Mark
dc.contributor.authorADAMS, Hieab
dc.contributor.authorBIS, Joshua C.
dc.contributor.authorSESHADRI, Sudha
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTZOURIO, Christophe
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorMAZOYER, Bernard
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.date.accessioned2021-12-06T10:58:10Z
dc.date.available2021-12-06T10:58:10Z
dc.date.issued2021-10-23
dc.identifier.issn2451-9030 (Electronic) 2451-9022 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/123987
dc.description.abstractEnBACKGROUND: Subcortical brain structures play a key role in pathological processes of age-related neurodegenerative disorders. Mounting evidence also suggests that early-life factors may have an impact on the development of common late-life neurological diseases, including genetic factors that can influence both brain maturation and neurodegeneration. METHODS: Using large population-based brain imaging datasets across the lifespan (N<40,628) we aimed to: (i) estimate the heritability of subcortical volumes in young (18-35), middle (35-65), and older age (65+), and their genetic correlation across age groups; (ii) identify whether genetic loci associated with subcortical volumes in older persons also show associations in early adulthood, and explore underlying genes using transcriptome-wide association studies; (iii) explore their association with neurological phenotypes. RESULTS: Heritability of subcortical volumes consistently decreased with increasing age. Genetic risk scores for smaller caudate nucleus, putamen and hippocampus volume in older adults were associated with smaller volumes in young adults. Individually, ten loci associated with subcortical volumes in older adults also showed associations in young adults. Within these loci, transcriptome-wide association studies showed that expression of several genes in brain tissues (especially MYLK2 and TUFM) was associated with subcortical volumes in both age-groups. One risk variant for smaller caudate nucleus volume (TUFM locus) was associated with lower cognitive performance. Genetically-predicted Alzheimer's disease was associated with smaller subcortical volumes in middle and older age. CONCLUSIONS: Our findings provide novel insights into the genetic determinants of subcortical volumes across the lifespan. More studies are needed to decipher the underlying biology and clinical impact.
dc.description.sponsorshipEtude de cohorte sur la santé des étudiants
dc.description.sponsorshipStopping cognitive decline and dementia by fighting covert cerebral small vessel disease
dc.language.isoENen_US
dc.subject.enGenomics
dc.subject.enEpidemiology
dc.subject.enLifecourse approach
dc.subject.enSubcortical volumes
dc.subject.enDementia
dc.title.enGenomic studies across the lifespan point to early mechanisms determining subcortical volumes
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.bpsc.2021.10.011en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed34700051en_US
dc.description.sponsorshipEuropeStudy on Environmental and GenomeWide predictors of early structural brain Alterations in Young students
dc.description.sponsorshipEuropeERA-NET for establishing synergies between the Joint Programming on Neurodegenerative Diseases Research and Horizon 2020
dc.description.sponsorshipEuropeCommon mechanisms and pathways in Stroke and Alzheimer's disease.
bordeaux.journalBiological Psychiatry: Cognitive Neuroscience and Neuroimagingen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamHEALTHY_BPH
bordeaux.teamVINTAGEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03466940
hal.version1
hal.date.transferred2021-12-06T10:58:13Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=Biological%20Psychiatry:%20Cognitive%20Neuroscience%20and%20Neuroimaging&amp;rft.date=2021-10-23&amp;rft.eissn=2451-9030%20(Electronic)%202451-9022%20(Linking)&amp;rft.issn=2451-9030%20(Electronic)%202451-9022%20(Linking)&amp;rft.au=LE%20GRAND,%20Quentin&amp;SATIZABAL,%20Claudia%20L.&amp;SARGURUPREMRAJ,%20Muralidharan&amp;MISHRA,%20Aniket&amp;SOUMARE,%20Aicha&amp;rft.genre=article


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