Afficher la notice abrégée

Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease

dc.rights.licenseopenen_US
dc.contributor.authorHOLSTEGE, Henne
dc.contributor.authorHULSMAN, Marc
dc.contributor.authorCHARBONNIER, Camille
dc.contributor.authorGRENIER-BOLEY, Benjamin
dc.contributor.authorQUENEZ, Olivier
dc.contributor.authorGROZEVA, Detelina
dc.contributor.authorVAN ROOIJ, Jeroen G. J.
dc.contributor.authorSIMS, Rebecca
dc.contributor.authorAHMAD, Shahzad
dc.contributor.authorAMIN, Najaf
dc.contributor.authorNORSWORTHY, Penny J.
dc.contributor.authorDOLS-ICARDO, Oriol
dc.contributor.authorHUMMERICH, Holger
dc.contributor.authorKAWALIA, Amit
dc.contributor.authorAMOUYEL, Philippe
dc.contributor.authorBEECHAM, Gary W.
dc.contributor.authorBERR, Claudine
dc.contributor.authorBIS, Joshua C.
dc.contributor.authorBOLAND, Anne
dc.contributor.authorBOSSÙ, Paola
dc.contributor.authorBOUWMAN, Femke
dc.contributor.authorBRAS, Jose
dc.contributor.authorCAMPION, Dominique
dc.contributor.authorCOCHRAN, J. Nicholas
dc.contributor.authorDANIELE, Antonio
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDARTIGUES, Jean-Francois
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorDELEUZE, Jean-Francois
dc.contributor.authorDENNING, Nicola
dc.contributor.authorDESTEFANO, Anita L.
dc.contributor.authorFARRER, Lindsay A.
dc.contributor.authorFERNANDEZ, Maria Victoria
dc.contributor.authorFOX, Nick C.
dc.contributor.authorGALIMBERTI, Daniela
dc.contributor.authorGENIN, Emmanuelle
dc.contributor.authorGILLE, Johan J. P.
dc.contributor.authorLE GUEN, Yann
dc.contributor.authorGUERREIRO, Rita
dc.contributor.authorHAINES, Jonathan L.
dc.contributor.authorHOLMES, Clive
dc.contributor.authorIKRAM, M. Arfan
dc.contributor.authorIKRAM, M. Kamran
dc.contributor.authorJANSEN, Iris E.
dc.contributor.authorKRAAIJ, Robert
dc.contributor.authorLATHROP, Marc
dc.contributor.authorLEMSTRA, Afina W.
dc.contributor.authorLLEO, Alberto
dc.contributor.authorLUCKCUCK, Lauren
dc.contributor.authorMANNENS, Marcel M. A. M.
dc.contributor.authorMARSHALL, Rachel
dc.contributor.authorMARTIN, Eden R.
dc.contributor.authorMASULLO, Carlo
dc.contributor.authorMAYEUX, Richard
dc.contributor.authorMECOCCI, Patrizia
dc.contributor.authorMEGGY, Alun
dc.contributor.authorMOL, Merel O.
dc.contributor.authorMORGAN, Kevin
dc.contributor.authorMYERS, Richard M.
dc.contributor.authorNACMIAS, Benedetta
dc.contributor.authorNAJ, Adam C.
dc.contributor.authorNAPOLIONI, Valerio
dc.contributor.authorPASQUIER, Florence
dc.contributor.authorPASTOR, Pau
dc.contributor.authorPERICAK-VANCE, Margaret A.
dc.contributor.authorRAYBOULD, Rachel
dc.contributor.authorREDON, Richard
dc.contributor.authorREINDERS, Marcel J. T.
dc.contributor.authorRICHARD, Anne-Claire
dc.contributor.authorRIEDEL-HELLER, Steffi G.
dc.contributor.authorRIVADENEIRA, Fernando
dc.contributor.authorROUSSEAU, Stephane
dc.contributor.authorRYAN, Natalie S.
dc.contributor.authorSAAD, Salha
dc.contributor.authorSANCHEZ-JUAN, Pascual
dc.contributor.authorSCHELLENBERG, Gerard D.
dc.contributor.authorSCHELTENS, Philip
dc.contributor.authorSCHOTT, Jonathan M.
dc.contributor.authorSERIPA, Davide
dc.contributor.authorSESHADRI, Sudha
dc.contributor.authorSIE, Daoud
dc.contributor.authorSISTERMANS, Erik A.
dc.contributor.authorSORBI, Sandro
dc.contributor.authorVAN SPAENDONK, Resie
dc.contributor.authorSPALLETTA, Gianfranco
dc.contributor.authorTESI, Niccolo’
dc.contributor.authorTIJMS, Betty
dc.contributor.authorUITTERLINDEN, Andre G.
dc.contributor.authorVAN DER LEE, Sven J.
dc.contributor.authorVISSER, Pieter Jelle
dc.contributor.authorWAGNER, Michael
dc.contributor.authorWALLON, David
dc.contributor.authorWANG, Li-San
dc.contributor.authorZAREA, Aline
dc.contributor.authorCLARIMON, Jordi
dc.contributor.authorVAN SWIETEN, John C.
dc.contributor.authorGREICIUS, Michael D.
dc.contributor.authorYOKOYAMA, Jennifer S.
dc.contributor.authorCRUCHAGA, Carlos
dc.contributor.authorHARDY, John
dc.contributor.authorRAMIREZ, Alfredo
dc.contributor.authorMEAD, Simon
dc.contributor.authorVAN DER FLIER, Wiesje M.
dc.contributor.authorVAN DUIJN, Cornelia M.
dc.contributor.authorWILLIAMS, Julie
dc.contributor.authorNICOLAS, Gael
dc.contributor.authorBELLENGUEZ, Celine
dc.contributor.authorLAMBERT, Jean-Charles
dc.date.accessioned2022-12-15T11:00:54Z
dc.date.available2022-12-15T11:00:54Z
dc.date.issued2022-11-21
dc.identifier.issn1546-1718 (Electronic) 1061-4036 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/171539
dc.description.abstractEnAlzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%(1). The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants(2). Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enExome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41588-022-01208-7en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed36411364en_US
bordeaux.journalNature Geneticsen_US
bordeaux.page1786-1794en_US
bordeaux.volume54en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamACTIVE_BPHen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03900692
hal.version1
hal.date.transferred2022-12-15T11:01:25Z
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%20Genetics&rft.date=2022-11-21&rft.volume=54&rft.spage=1786-1794&rft.epage=1786-1794&rft.eissn=1546-1718%20(Electronic)%201061-4036%20(Linking)&rft.issn=1546-1718%20(Electronic)%201061-4036%20(Linking)&rft.au=HOLSTEGE,%20Henne&HULSMAN,%20Marc&CHARBONNIER,%20Camille&GRENIER-BOLEY,%20Benjamin&QUENEZ,%20Olivier&rft.genre=article


Fichier(s) constituant ce document

Thumbnail
Nom:
BPH_NG_2022_Holstege.pdf
Taille:
7.925Mo
Format:
PDF
Voir/Ouvrir
Thumbnail
Nom:
license_rdf
Taille:
914octets
Format:
application/rdf+xml
Voir/Ouvrir

Ce document figure dans la(les) collection(s) suivante(s)

Afficher la notice abrégée