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Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities

dc.rights.licenseopenen_US
dc.contributor.authorARMSTRONG, N. J.
dc.contributor.authorMATHER, K. A.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSARGURUPREMRAJ, Muralidharan
dc.contributor.authorKNOL, M. J.
dc.contributor.authorMALIK, R.
dc.contributor.authorSATIZABAL, C. L.
dc.contributor.authorYANEK, L. R.
dc.contributor.authorWEN, W.
dc.contributor.authorGUDNASON, V. G.
dc.contributor.authorDUEKER, N. D.
dc.contributor.authorELLIOTT, L. T.
dc.contributor.authorHOFER, E.
dc.contributor.authorBIS, J.
dc.contributor.authorJAHANSHAD, N.
dc.contributor.authorLI, S.
dc.contributor.authorLOGUE, M. A.
dc.contributor.authorLUCIANO, M.
dc.contributor.authorSCHOLZ, M.
dc.contributor.authorSMITH, A. V.
dc.contributor.authorTROMPET, S.
dc.contributor.authorVOJINOVIC, D.
dc.contributor.authorXIA, R.
dc.contributor.authorALFARO-ALMAGRO, F.
dc.contributor.authorAMES, D.
dc.contributor.authorAMIN, N.
dc.contributor.authorAMOUYEL, Philippe
dc.contributor.authorBEISER, A. S.
dc.contributor.authorBRODATY, H.
dc.contributor.authorDEARY, I. J.
dc.contributor.authorFENNEMA-NOTESTINE, C.
dc.contributor.authorGAMPAWAR, P. G.
dc.contributor.authorGOTTESMAN, R.
dc.contributor.authorGRIFFANTI, L.
dc.contributor.authorJACK, Jr., C. R.
dc.contributor.authorJENKINSON, M.
dc.contributor.authorJIANG, J.
dc.contributor.authorKRAL, B. G.
dc.contributor.authorKWOK, J. B.
dc.contributor.authorLAMPE, L.
dc.contributor.authorD, C. M. Liewald
dc.contributor.authorMAILLARD, P.
dc.contributor.authorMARCHINI, J.
dc.contributor.authorBASTIN, M. E.
dc.contributor.authorMAZOYER, Bernard
dc.contributor.authorPIRPAMER, L.
dc.contributor.authorRAFAEL ROMERO, J.
dc.contributor.authorROSHCHUPKIN, G. V.
dc.contributor.authorSCHOFIELD, P. R.
dc.contributor.authorSCHROETER, M. L.
dc.contributor.authorSTOTT, D. J.
dc.contributor.authorTHALAMUTHU, A.
dc.contributor.authorTROLLOR, J.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTZOURIO, Christophe
dc.contributor.authorVAN DER GROND, J.
dc.contributor.authorVERNOOIJ, M. W.
dc.contributor.authorWITTE, V. A.
dc.contributor.authorWRIGHT, M. J.
dc.contributor.authorYANG, Q.
dc.contributor.authorMORRIS, Z.
dc.contributor.authorSIGGURDSSON, S.
dc.contributor.authorPSATY, B.
dc.contributor.authorVILLRINGER, A.
dc.contributor.authorSCHMIDT, H.
dc.contributor.authorHABERG, A. K.
dc.contributor.authorVAN DUIJN, C. M.
dc.contributor.authorJUKEMA, J. W.
dc.contributor.authorDICHGANS, M.
dc.contributor.authorSACCO, R. L.
dc.contributor.authorWRIGHT, C. B.
dc.contributor.authorKREMEN, W. S.
dc.contributor.authorBECKER, L. C.
dc.contributor.authorTHOMPSON, P. M.
dc.contributor.authorMOSLEY, T. H.
dc.contributor.authorWARDLAW, J. M.
dc.contributor.authorIKRAM, M. A.
dc.contributor.authorADAMS, H. H. H.
dc.contributor.authorSESHADRI, Sudha
dc.contributor.authorSACHDEV, P. S.
dc.contributor.authorSMITH, S. M.
dc.contributor.authorLAUNER, L.
dc.contributor.authorLONGSTRETH, W.
dc.contributor.authorDECARLI, C.
dc.contributor.authorSCHMIDT, R.
dc.contributor.authorFORNAGE, M.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorNYQUIST, P. A.
dc.date.accessioned2021-01-26T10:35:09Z
dc.date.available2021-01-26T10:35:09Z
dc.date.issued2020
dc.identifier.issn1524-4628 (Electronic) 0039-2499 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26006
dc.description.abstractEnBackground and Purpose: Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings. Methods: Participants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC. Results: In the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 (NBEAL), 10q23.1 (TSPAN14/FAM231A), and 10q24.33 (SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 (NOS3) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype. Conclusions: Our study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.
dc.language.isoENen_US
dc.subjectHEALTHY
dc.subjectVINTAGE
dc.title.enCommon Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities
dc.title.alternativeStrokeen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1161/strokeaha.119.027544en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed32517579en_US
bordeaux.journalStrokeen_US
bordeaux.page2111-2121en_US
bordeaux.volume51en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue7en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamHEALTHY_BPHen_US
bordeaux.teamVINTAGEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03121237
hal.version1
hal.date.transferred2021-01-26T10:35:21Z
hal.exporttrue
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