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Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

dc.rights.licenseopenen_US
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorCHAUHAN, Ganesh
dc.contributor.authorADAMS, Hieab
dc.contributor.authorSATIZABAL, Claudia
dc.contributor.authorBIS, Joshua
dc.contributor.authorTEUMER, Alexander
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSARGURUPREMRAJ, Muralidharan
dc.contributor.authorHOFER, Edith
dc.contributor.authorTROMPET, Stella
dc.contributor.authorHILAL, Saima
dc.contributor.authorSMITH, Albert
dc.contributor.authorJIAN, Xueqiu
dc.contributor.authorMALIK, Rainer
dc.contributor.authorTRAYLOR, Matthew
dc.contributor.authorPULIT, Sara
dc.contributor.authorAMOUYEL, Philippe
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMAZOYER, Bernard
dc.contributor.authorZHU, Yi-Cheng
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorKAFFASHIAN, Sara
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSCHILLING, Sabrina
dc.contributor.authorBEECHAM, Gary
dc.contributor.authorMONTINE, Thomas
dc.contributor.authorSCHELLENBERG, Gerard
dc.contributor.authorKJARTANSSON, Olafur
dc.contributor.authorGUÐNASON, Vilmundur
dc.contributor.authorKNOPMAN, David
dc.contributor.authorGRISWOLD, Michael
dc.contributor.authorWINDHAM, B
dc.contributor.authorGOTTESMAN, Rebecca
dc.contributor.authorMOSLEY, Thomas
dc.contributor.authorSCHMIDT, Reinhold
dc.contributor.authorSABA, Yasaman
dc.contributor.authorSCHMIDT, Helena
dc.contributor.authorTAKEUCHI, Fumihiko
dc.contributor.authorYAMAGUCHI, Shuhei
dc.contributor.authorNABIKA, Toru
dc.contributor.authorKATO, Norihiro
dc.contributor.authorRAJAN, Kumar
dc.contributor.authorAGGARWAL, Neelum
dc.contributor.authorDE JAGER, Philip
dc.contributor.authorEVANS, Denis
dc.contributor.authorPSATY, Bruce
dc.contributor.authorROTTER, Jerome
dc.contributor.authorRICE, Kenneth
dc.contributor.authorLOPEZ, Oscar
dc.contributor.authorLIAO, Jiemin
dc.contributor.authorMA, Christopher
dc.contributor.authorCHEN, Ching-Yu
dc.contributor.authorCHENG, Tien
dc.contributor.authorWONG, Mohammad
dc.contributor.authorIKRAM, Sven
dc.contributor.authorVAN DER LEE, Najaf
dc.contributor.authorAMIN, Vincent
dc.contributor.authorCHOURAKI, Anita
dc.contributor.authorDESTEFANO, Hugo
dc.contributor.authorAPARICIO, Jose
dc.contributor.authorROMERO, Pauline
dc.contributor.authorMAILLARD, Charles
dc.contributor.authorDECARLI, Joanna
dc.contributor.authorWARDLAW, Maria
dc.contributor.authorVALDÉS HERNÁNDEZ, Michelle
dc.contributor.authorLUCIANO, David
dc.contributor.authorLIEWALD, Ian
dc.contributor.authorDEARY, John
dc.contributor.authorSTARR, Mark
dc.contributor.authorBASTIN, Susana
dc.contributor.authorSLAGBOOM, Marian
dc.contributor.authorBEEKMAN, Joris
dc.contributor.authorDEELEN, Hae-Won
dc.contributor.authorUH, Robin
dc.contributor.authorLEMMENS, Henry
dc.contributor.authorBRODATY, Margaret
dc.contributor.authorWRIGHT, David
dc.contributor.authorAMES, Giorgio
dc.contributor.authorBONCORAGLIO, Jemma
dc.contributor.authorHOPEWELL, Ashley
dc.contributor.authorBEECHAM, Susan
dc.contributor.authorBLANTON, Clinton
dc.contributor.authorWRIGHT, Ralph
dc.contributor.authorSACCO, Wei
dc.contributor.authorWEN, Anbupalam
dc.contributor.authorTHALAMUTHU, Nicola
dc.contributor.authorARMSTRONG, Elizabeth
dc.contributor.authorCHONG, Peter
dc.contributor.authorSCHOFIELD, John
dc.contributor.authorKWOK, Jeroen
dc.contributor.authorVAN DER GROND, David
dc.contributor.authorSTOTT, Ian
dc.contributor.authorFORD, J
dc.contributor.authorJUKEMA, Meike
dc.contributor.authorVERNOOIJ, Albert
dc.contributor.authorHOFMAN, André
dc.contributor.authorUITTERLINDEN, Aad
dc.contributor.authorVAN DER LUGT, Katharina
dc.contributor.authorWITTFELD, Hans
dc.contributor.authorGRABE, Norbert
dc.contributor.authorHOSTEN, Bettina
dc.contributor.authorVON SARNOWSKI, Uwe
dc.contributor.authorVÖLKER, Christopher
dc.contributor.authorLEVI, Jordi
dc.contributor.authorJIMENEZ-CONDE, Pankaj
dc.contributor.authorSUDLOW, Cathie
dc.contributor.authorROSAND, Jonathan
dc.contributor.authorWOO, Daniel
dc.contributor.authorCOLE, John
dc.contributor.authorMESCHIA, James
dc.contributor.authorSLOWIK, Agnieszka
dc.contributor.authorTHIJS, Vincent
dc.contributor.authorLINDGREN, Arne
dc.contributor.authorMELANDER, Olle
dc.contributor.authorGREWAL, Raji
dc.contributor.authorRUNDEK, Tatjana
dc.contributor.authorREXRODE, Kathy
dc.contributor.authorROTHWELL, Peter
dc.contributor.authorARNETT, Donna
dc.contributor.authorJERN, Christina
dc.contributor.authorJOHNSON, Julie
dc.contributor.authorBENAVENTE, Oscar
dc.contributor.authorWASSSERTHEIL-SMOLLER, Sylvia
dc.contributor.authorLEE, Jin-Moo
dc.contributor.authorWONG, Quenna
dc.contributor.authorMITCHELL, Braxton
dc.contributor.authorRICH, Stephen
dc.contributor.authorMCARDLE, Patrick
dc.contributor.authorGEERLINGS, Mirjam
dc.contributor.authorVAN DER GRAAF, Yolanda
dc.contributor.authorDE BAKKER, Paul
dc.contributor.authorASSELBERGS, Folkert
dc.contributor.authorSRIKANTH, Velandai
dc.contributor.authorTHOMSON, Russell
dc.contributor.authorMCWHIRTER, Rebekah
dc.contributor.authorMORAN, Chris
dc.contributor.authorCALLISAYA, Michele
dc.contributor.authorPHAN, Thanh
dc.contributor.authorLOES, C
dc.contributor.authorRUTTEN-JACOBS, Steve
dc.contributor.authorBEVAN, Christophe
dc.contributor.authorMATHER, Karen
dc.contributor.authorSACHDEV, Perminder
dc.contributor.authorVAN DUIJN, Cornelia
dc.contributor.authorWORRALL, Bradford
dc.contributor.authorDICHGANS, Martin
dc.contributor.authorKITTNER, Steven
dc.contributor.authorMARKUS, Hugh
dc.contributor.authorFMEDSCI, Mohammad
dc.contributor.authorFORNAGE, Myriam
dc.contributor.authorLAUNER, Lenore
dc.contributor.authorSESHADRI, Sudha
dc.contributor.authorLONGSTRETH, W
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.date.accessioned2021-04-30T09:30:40Z
dc.date.available2021-04-30T09:30:40Z
dc.date.issued2019
dc.identifier.issn0028-3878en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/27138
dc.description.abstractEnObjective: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.Methods: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.Results: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy.Conclusion: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.
dc.language.isoENen_US
dc.title.enGenetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting
dc.typeArticle de revueen_US
dc.identifier.doi10.1212/WNL.0000000000006851en_US
dc.subject.halSciences du Vivant [q-bio]en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed30651383en_US
bordeaux.journalNeurologyen_US
bordeaux.pagee486-e503en_US
bordeaux.volume92en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamVINTAGEen_US
bordeaux.teamVINTAGEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierinserm-02457571
hal.version1
hal.exportfalse
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