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Cerebral small vessel disease genomics and its implications across the lifespan

dc.rights.licenseopenen_US
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSARGURUPREMRAJ, Muralidharan
dc.contributor.authorSUZUKI, H.
dc.contributor.authorJIAN, X.
dc.contributor.authorSARNOWSKI, C.
dc.contributor.authorEVANS, T. E.
dc.contributor.authorBIS, J. C.
dc.contributor.authorEIRIKSDOTTIR, G.
dc.contributor.authorSAKAUE, S.
dc.contributor.authorTERZIKHAN, N.
dc.contributor.authorHABES, M.
dc.contributor.authorZHAO, W.
dc.contributor.authorARMSTRONG, N. J.
dc.contributor.authorHOFER, E.
dc.contributor.authorYANEK, L. R.
dc.contributor.authorHAGENAARS, S. P.
dc.contributor.authorKUMAR, R. B.
dc.contributor.authorVAN DEN AKKER, E. B.
dc.contributor.authorMCWHIRTER, R. E.
dc.contributor.authorTROMPET, S.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMISHRA, Aniket
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSABA, Yasaman
dc.contributor.authorSATIZABAL, C. L.
dc.contributor.authorBEAUDET, G.
dc.contributor.authorPETIT, L.
dc.contributor.authorTSUCHIDA, A.
dc.contributor.authorZAGO, L.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSCHILLING, Sabrina
dc.contributor.authorSIGURDSSON, S.
dc.contributor.authorGOTTESMAN, R. F.
dc.contributor.authorLEWIS, C. E.
dc.contributor.authorAGGARWAL, N. T.
dc.contributor.authorLOPEZ, O. L.
dc.contributor.authorSMITH, J. A.
dc.contributor.authorVALDES HERNANDEZ, M. C.
dc.contributor.authorVAN DER GROND, J.
dc.contributor.authorWRIGHT, M. J.
dc.contributor.authorKNOL, M. J.
dc.contributor.authorDORR, M.
dc.contributor.authorTHOMSON, R. J.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBORDES, Constance
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorLE GRAND, Quentin
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDUPERRON, Marie-Gabrielle
dc.contributor.authorSMITH, A. V.
dc.contributor.authorKNOPMAN, D. S.
dc.contributor.authorSCHREINER, P. J.
dc.contributor.authorEVANS, D. A.
dc.contributor.authorROTTER, J. I.
dc.contributor.authorBEISER, A. S.
dc.contributor.authorMANIEGA, S. M.
dc.contributor.authorBEEKMAN, M.
dc.contributor.authorTROLLOR, J.
dc.contributor.authorSTOTT, D. J.
dc.contributor.authorVERNOOIJ, M. W.
dc.contributor.authorWITTFELD, K.
dc.contributor.authorNIESSEN, W. J.
dc.contributor.authorSOUMARE, A.
dc.contributor.authorBOERWINKLE, E.
dc.contributor.authorSIDNEY, S.
dc.contributor.authorTURNER, S. T.
dc.contributor.authorDAVIES, G.
dc.contributor.authorTHALAMUTHU, A.
dc.contributor.authorVOLKER, U.
dc.contributor.authorVAN BUCHEM, M. A.
dc.contributor.authorBRYAN, R. N.
dc.contributor.authorDUPUIS, J.
dc.contributor.authorBASTIN, M. E.
dc.contributor.authorAMES, D.
dc.contributor.authorTEUMER, A.
dc.contributor.authorAMOUYEL, Philippe
dc.contributor.authorKWOK, J. B.
dc.contributor.authorBULOW, R.
dc.contributor.authorDEARY, I. J.
dc.contributor.authorSCHOFIELD, P. R.
dc.contributor.authorBRODATY, H.
dc.contributor.authorJIANG, J.
dc.contributor.authorTABARA, Y.
dc.contributor.authorSETOH, K.
dc.contributor.authorMIYAMOTO, S.
dc.contributor.authorYOSHIDA, K.
dc.contributor.authorNAGATA, M.
dc.contributor.authorKAMATANI, Y.
dc.contributor.authorMATSUDA, F.
dc.contributor.authorPSATY, B. M.
dc.contributor.authorBENNETT, D. A.
dc.contributor.authorDE JAGER, P. L.
dc.contributor.authorMOSLEY, T. H.
dc.contributor.authorSACHDEV, P. S.
dc.contributor.authorSCHMIDT, R.
dc.contributor.authorWARREN, H. R.
dc.contributor.authorEVANGELOU, E.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTREGOUET, David-Alexandre
dc.contributor.authorINTERNATIONAL NETWORK AGAINST THROMBOSIS, Consortium
dc.contributor.authorINTERNATIONAL HEADACHE GENOMICS, Consortium
dc.contributor.authorIKRAM, M. A.
dc.contributor.authorWEN, W.
dc.contributor.authorDECARLI, C.
dc.contributor.authorSRIKANTH, V. K.
dc.contributor.authorJUKEMA, J. W.
dc.contributor.authorSLAGBOOM, E. P.
dc.contributor.authorKARDIA, S. L. R.
dc.contributor.authorOKADA, Y.
dc.contributor.authorMAZOYER, Bernard
dc.contributor.authorWARDLAW, J. M.
dc.contributor.authorNYQUIST, P. A.
dc.contributor.authorMATHER, K. A.
dc.contributor.authorGRABE, H. J.
dc.contributor.authorSCHMIDT, H.
dc.contributor.authorVAN DUIJN, C. M.
dc.contributor.authorGUDNASON, V.
dc.contributor.authorLONGSTRETH, W. T., Jr.
dc.contributor.authorLAUNER, L. J.
dc.contributor.authorLATHROP, M.
dc.contributor.authorSESHADRI, Sudha
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTZOURIO, Christophe
dc.contributor.authorADAMS, H. H.
dc.contributor.authorMATTHEWS, P. M.
dc.contributor.authorFORNAGE, M.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.date.accessioned2021-03-08T10:51:57Z
dc.date.available2021-03-08T10:51:57Z
dc.date.issued2020-12-08
dc.identifier.issn2041-1723 (Electronic) 2041-1723 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26449
dc.description.abstractEnWhite matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5x10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enCerebral small vessel disease genomics and its implications across the lifespan
dc.title.alternativeNat Communen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41467-020-19111-2en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed33293549en_US
bordeaux.journalNature Communicationsen_US
bordeaux.page6285en_US
bordeaux.volume11en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamVINTAGEen_US
bordeaux.teamHEALTHY_BPH
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature%20Communications&rft.date=2020-12-08&rft.volume=11&rft.issue=1&rft.spage=6285&rft.epage=6285&rft.eissn=2041-1723%20(Electronic)%202041-1723%20(Linking)&rft.issn=2041-1723%20(Electronic)%202041-1723%20(Linking)&rft.au=SARGURUPREMRAJ,%20Muralidharan&SUZUKI,%20H.&JIAN,%20X.&SARNOWSKI,%20C.&EVANS,%20T.%20E.&rft.genre=article


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