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Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities

dc.rights.licenseopenen_US
dc.contributor.authorFRANCIS, Catherine M.
dc.contributor.authorFUTSCHIK, Matthias E.
dc.contributor.authorHUANG, Jian
dc.contributor.authorBAI, Wenjia
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSARGURUPREMRAJ, Muralidharan
dc.contributor.authorTEUMER, Alexander
dc.contributor.authorBRETELER, Monique M. B.
dc.contributor.authorPETRETTO, Enrico
dc.contributor.authorHO, Amanda S. R.
dc.contributor.authorAMOUYEL, Philippe
dc.contributor.authorENGELTER, Stefan T.
dc.contributor.authorBULOW, Robin
dc.contributor.authorVOLKER, Uwe
dc.contributor.authorVOLZKE, Henry
dc.contributor.authorDORR, Marcus
dc.contributor.authorIMTIAZ, Mohammed-Aslam
dc.contributor.authorAZIZ, N. Ahmad
dc.contributor.authorLOHNER, Valerie
dc.contributor.authorWARE, James S.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorELLIOTT, Paul
dc.contributor.authorDEHGHAN, Abbas
dc.contributor.authorMATTHEWS, Paul M.
dc.date.accessioned2022-10-27T07:57:58Z
dc.date.available2022-10-27T07:57:58Z
dc.date.issued2022-08-03
dc.identifier.issn2041-1723en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/170121
dc.description.abstractEnAortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-beta, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease.
dc.description.sponsorshipStopping cognitive decline and dementia by fighting covert cerebral small vessel disease - ANR-18-RHUS-0002en_US
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enGenome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41467-022-32219-xen_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed35922433en_US
dc.description.sponsorshipEuropeStudy on Environmental and GenomeWide predictors of early structural brain Alterations in Young studentsen_US
dc.description.sponsorshipEuropeCommon mechanisms and pathways in Stroke and Alzheimer's disease.en_US
dc.description.sponsorshipEuropePREvention of STroke in Intracerebral haemorrhaGE survivors with Atrial Fibrillationen_US
bordeaux.journalNature Communicationsen_US
bordeaux.volume13en_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.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDAgence Nationale de la Rechercheen_US
bordeaux.identifier.funderIDEuropean Research Councilen_US
hal.identifierhal-03831624
hal.version1
hal.date.transferred2022-10-27T07:58:26Z
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%20Communications&rft.date=2022-08-03&rft.volume=13&rft.issue=1&rft.eissn=2041-1723&rft.issn=2041-1723&rft.au=FRANCIS,%20Catherine%20M.&FUTSCHIK,%20Matthias%20E.&HUANG,%20Jian&BAI,%20Wenjia&SARGURUPREMRAJ,%20Muralidharan&rft.genre=article


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