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APOE stratified genome-wide association studies provide novel insights into the genetic etiology of Alzheimers's disease

dc.rights.licenseopenen_US
dc.contributor.authorTHOMASSEN, Jesper Qvist
dc.contributor.authorHAMPTON, Leonard
dc.contributor.authorULMS, Brittany
dc.contributor.authorGRENIER-BOLEY, Benjamin
dc.contributor.authorHEIKKINEN, Sami
dc.contributor.authorGARCIA, Pablo
dc.contributor.authorCASTILLO-MORALES, Atahualapa
dc.contributor.authorKIKUCHI, Masataka
dc.contributor.authorGIM, Jungsoo
dc.contributor.authorCAO, Han
dc.contributor.authorKUCUKALI, Fahri
dc.contributor.authorAMIN, Najaf
dc.contributor.authorYOON, Dabin
dc.contributor.authorDE ROJAS, Itziar
dc.contributor.authorJEREZ, Pilar Alvarez
dc.contributor.authorALVAREZ, Victoria
dc.contributor.authorAROSIO, Beatrice
dc.contributor.authorBELLENGUEZ, Celine
dc.contributor.authorBERGH, Sverre
dc.contributor.authorBILLINGSLEY, Kimberly
dc.contributor.authorBLAUWENDRAAT, Cornelis
dc.contributor.authorBOADA, Merce
dc.contributor.authorBORRONI, Barbara
dc.contributor.authorBOSSU, Paola
dc.contributor.authorBULLIDO, Maria J
dc.contributor.authorDANIELE, Antonio
dc.contributor.authorCARRACEDO, Angel
dc.contributor.authorDE MENDONCA, Alexandre
dc.contributor.authorCOOKSON, Mark
dc.contributor.authorDECKERT, Jurgen
dc.contributor.authorDICHGANS, Martin
dc.contributor.authorDJUROVIC, Srdjan
dc.contributor.authorDOLS-ICARDO, Oriol
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDUFOUIL, Carole
dc.contributor.authorDUZEL, Emrah
dc.contributor.authorESCOTT-PRICE, Valentina
dc.contributor.authorFLADBY, Tormod
dc.contributor.authorFRATIGLIONI, Laura
dc.contributor.authorFU, Amy K Y
dc.contributor.authorGALIMBERTI, Daniela
dc.contributor.authorGARCIA-ALBERCA, Jose Maria
dc.contributor.authorGIEDRAITIS, Vilmantas
dc.contributor.authorGARCIA-RIBAS, Guillermo
dc.contributor.authorGRAFF, Caroline
dc.contributor.authorGRIMMER, Timo
dc.contributor.authorGRUNBLATT, Edna
dc.contributor.authorHANON, OIivier
dc.contributor.authorHAUSNER, Lucrezia
dc.contributor.authorHEILMANN-HEMIBACH, Stefanie
dc.contributor.authorHORT, Jakub
dc.contributor.authorJESSEN, Frank
dc.contributor.authorJENSEN, Kendall
dc.contributor.authorJONSON, Caroline
dc.contributor.authorKIM, Yoontae
dc.contributor.authorKUZNETSOV, Nicole
dc.contributor.authorLEINONEN, Ville
dc.contributor.authorLIPPONEN, Anssi
dc.contributor.authorLUO, Jiao
dc.contributor.authorMAKARIOUS, Mary
dc.contributor.authorMARTISKAINEN, Henna
dc.contributor.authorMASULLO, Carlo
dc.contributor.authorMECOCCI, Patrizia
dc.contributor.authorMEHRABIAN, Shima
dc.contributor.authorMIR, Pablo
dc.contributor.authorMIYASHITA, Akinori
dc.contributor.authorMOEBUS, Susanne
dc.contributor.authorMOK, Kin Y
dc.contributor.authorPORCEL, Laura Molina
dc.contributor.authorMORENO, Fermin
dc.contributor.authorNACMIAS, Benedetta
dc.contributor.authorPARNETTI, Lucilla
dc.contributor.authorPASTOR, Pau
dc.contributor.authorPEREZ-TUR, Jordi
dc.contributor.authorPETERS, Oliver
dc.contributor.authorPIJNENBURG, Yolande A L
dc.contributor.authorPINOL-RIPOLL, Gerard
dc.contributor.authorPOPP, Julius
dc.contributor.authorRAINERO, Innocenzo
dc.contributor.authorREAL, Luis M
dc.contributor.authorRIEDEL-HELLER, Steffi
dc.contributor.authorRODRIGUEZ-RODRIGUEZ, Eloy
dc.contributor.authorRONGVE, Arvid
dc.contributor.authorROSSI, Giacomina
dc.contributor.authorROYO, Jose Luis
dc.contributor.authorRUJESCU, Dan
dc.contributor.authorSALTVEDT, Ingvild
dc.contributor.authorSAEZ, Maria Eugenia
dc.contributor.authorSANCHEZ-VALLE, Raquel
dc.contributor.authorSANCHEZ-GARCIA, Florentino
dc.contributor.authorSANDAU, Nicolai
dc.contributor.authorSCARMEAS, Nikolaos
dc.contributor.authorSCHEFFLER, Katja
dc.contributor.authorSCHERBAUM, Norbert
dc.contributor.authorSCHNEIDER, Anja
dc.contributor.authorSELBAEK, Geir
dc.contributor.authorSERIPA, Davide
dc.contributor.authorSOLFRIZZI, Vincenzo
dc.contributor.authorSPALLAZZI, Marco
dc.contributor.authorSQUASSINA, Alessio
dc.contributor.authorSTORDAL, Eystein
dc.contributor.authorTESI, Niccolo
dc.contributor.authorTREMOLIZZO, Lucio
dc.contributor.authorTRIPATHI, Kumar P
dc.contributor.authorVAN DER FLIER, Wiesje M
dc.contributor.authorWILLIAMS, Julie
dc.contributor.authorWILTFANG, Jens
dc.contributor.authorAARSLAND, Dag
dc.contributor.authorSINGLETON, Andrew B
dc.contributor.authorAMOUYEL, Philippe
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorNICOLAS, Gael
dc.contributor.authorVAN DER LEE, Sven
dc.contributor.authorHOLSTEGE, Henne
dc.contributor.authorFERNANDEZ, Maria Victoria
dc.contributor.authorKEHOE, Patrick Gavin
dc.contributor.authorSLEEGERS, Kristel
dc.contributor.authorINGELSSON, Martin
dc.contributor.authorGHIDONI, Roberta
dc.contributor.authorANDREASSEN, Ole A
dc.contributor.authorHOLMANS, Peter A
dc.contributor.authorSANCHEZ-JUAN, Pascual
dc.contributor.authorSIMS, Rebecca
dc.contributor.authorIP, Nancy Y
dc.contributor.authorLEE, Kun Ho
dc.contributor.authorIKEUCHI, Takeshi
dc.contributor.authorRAMIREZ, Alfredo
dc.contributor.authorRUIZ, Agustin
dc.contributor.authorHILTUNEN, Mikko
dc.contributor.authorLAMBERT, Jean-Charles
dc.contributor.authorVAN DUIJN, Cornelia
dc.contributor.authorNALLS, Mike
dc.contributor.authorFRIKKE-SCHMIDT, Ruth
dc.date.accessioned2025-07-10T09:34:40Z
dc.date.available2025-07-10T09:34:40Z
dc.date.issued2025-05-09
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/207295
dc.description.abstractEnAmong the more than 90 identified genetic risk loci for late-onset Alzheimer's disease (AD) and related dementias, the apolipoprotein E gene (APOE) ε2/ε3/ε4 polymorphism remains the longstanding benchmark for genetic disease risk with a consistently large effect across studies(1-10). Despite this massive signal, the exact mechanisms for how ε4 increases and for how ε2 decreases dementia risk is not well-understood. Importantly, recent trials of anti-amyloid therapies suggest less efficacy and higher risks of severe side effects in s4 carriers(11-13), hampering the treatment of those with the highest unmet need. To improve our understanding of the genetic architecture of AD in the context of its main genetic driver, we performed genome-wide association studies (GWASs) stratified by ε4 and ε2 carrier status. Such insights may help to understand and overcome side effects, to impact clinical trial enrolment strategies, and to create the scientific basis for targeted mechanism-driven therapies in neurodegenerative diseases.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.title.enAPOE stratified genome-wide association studies provide novel insights into the genetic etiology of Alzheimers's disease
dc.title.alternativemedRxiv
dc.typeDocument de travail - Pré-publicationen_US
dc.identifier.doi10.1101/2025.05.07.25327065en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed40385391en_US
bordeaux.journalmedRxiv : the preprint server for health sciencesen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamPHARES_BPHen_US
bordeaux.teamELEANOR_BPHen_US
hal.identifierhal-05156070
hal.version1
hal.date.transferred2025-07-10T09:34:54Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.subtypePrepublication/Preprinten_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=medRxiv%20:%20the%20preprint%20server%20for%20health%20sciences&rft.date=2025-05-09&rft.au=THOMASSEN,%20Jesper%20Qvist&HAMPTON,%20Leonard&ULMS,%20Brittany&GRENIER-BOLEY,%20Benjamin&HEIKKINEN,%20Sami&rft.genre=preprint


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