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Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease.

dc.rights.licenseopenen_US
dc.contributor.authorALI, Muhammad
dc.contributor.authorARCHER, Derek B
dc.contributor.authorGORIJALA, Priyanka
dc.contributor.authorWESTERN, Daniel
dc.contributor.authorTIMSINA, Jigyasha
dc.contributor.authorFERNÁNDEZ, Maria V
dc.contributor.authorWANG, Ting-Chen
dc.contributor.authorSATIZABAL, Claudia L
dc.contributor.authorYANG, Qiong
dc.contributor.authorBEISER, Alexa S
dc.contributor.authorWANG, Ruiqi
dc.contributor.authorCHEN, Gengsheng
dc.contributor.authorGORDON, Brian
dc.contributor.authorBENZINGER, Tammie L S
dc.contributor.authorXIONG, Chengjie
dc.contributor.authorMORRIS, John C
dc.contributor.authorBATEMAN, Randall J
dc.contributor.authorKARCH, Celeste M
dc.contributor.authorMCDADE, Eric
dc.contributor.authorGOATE, Alison
dc.contributor.authorSESHADRI, Sudha
dc.contributor.authorMAYEUX, Richard P
dc.contributor.authorSPERLING, Reisa A
dc.contributor.authorBUCKLEY, Rachel F
dc.contributor.authorJOHNSON, Keith A
dc.contributor.authorWON, Hong-Hee
dc.contributor.authorJUNG, Sang-Hyuk
dc.contributor.authorKIM, Hang-Rai
dc.contributor.authorSEO, Sang Won
dc.contributor.authorKIM, Hee Jin
dc.contributor.authorMORMINO, Elizabeth
dc.contributor.authorLAWS, Simon M
dc.contributor.authorFAN, Kang-Hsien
dc.contributor.authorKAMBOH, M Ilyas
dc.contributor.authorVEMURI, Prashanthi
dc.contributor.authorRAMANAN, Vijay K
dc.contributor.authorYANG, Hyun-Sik
dc.contributor.authorWENZEL, Allen
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorRAJULA, Hema Sekhar Reddy
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMISHRA, Aniket
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDUFOUIL, Carole
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorLOPEZ, Oscar L
dc.contributor.authorDEKOSKY, Steven T
dc.contributor.authorTAO, Feifei
dc.contributor.authorNAGLE, Michael W
dc.contributor.authorHOHMAN, Timothy J
dc.contributor.authorSUNG, Yun Ju
dc.contributor.authorDUMITRESCU, Logan
dc.contributor.authorCRUCHAGA, Carlos
dc.date.accessioned2023-10-04T13:39:26Z
dc.date.available2023-10-04T13:39:26Z
dc.date.issued2023-04-26
dc.identifier.issn2051-5960en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/184317
dc.description.abstractEnAmyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (Aβ) deposits in the brain and to study Alzheimer's disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong APOE signal on chr19q.13.32 (top SNP: APOE ɛ4; rs429358; β = 0.35, SE = 0.01, P = 6.2 × 10, MAF = 0.19), driven by APOE ɛ4, and five additional novel associations (APOE ε2/rs7412; rs73052335/rs5117, rs1081105, rs438811, and rs4420638) independent of APOE ɛ4. APOE ɛ4 and ε2 showed race specific effect with stronger association in Non-Hispanic Whites, with the lowest association in Asians. Besides the APOE, we also identified three other genome-wide loci: ABCA7 (rs12151021/chr19p.13.3; β = 0.07, SE = 0.01, P = 9.2 × 10, MAF = 0.32), CR1 (rs6656401/chr1q.32.2; β = 0.1, SE = 0.02, P = 2.4 × 10, MAF = 0.18) and FERMT2 locus (rs117834516/chr14q.22.1; β = 0.16, SE = 0.03, P = 1.1 × 10, MAF = 0.06) that all colocalized with AD risk. Sex-stratified analyses identified two novel female-specific signals on chr5p.14.1 (rs529007143, β = 0.79, SE = 0.14, P = 1.4 × 10, MAF = 0.006, sex-interaction P = 9.8 × 10) and chr11p.15.2 (rs192346166, β = 0.94, SE = 0.17, P = 3.7 × 10, MAF = 0.004, sex-interaction P = 1.3 × 10). We also demonstrated that the overall genetic architecture of brain amyloidosis overlaps with that of AD, Frontotemporal Dementia, stroke, and brain structure-related complex human traits. Overall, our results have important implications when estimating the individual risk to a population level, as race and sex will needed to be taken into account. This may affect participant selection for future clinical trials and therapies.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enHumans
dc.subject.enFemale
dc.subject.enAlzheimer Disease
dc.subject.enAmyloid beta-Peptides
dc.subject.enGenome-Wide Association Study
dc.subject.enAmyloidosis
dc.subject.enAmyloid
dc.subject.enApolipoproteins E
dc.title.enLarge multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease.
dc.title.alternativeActa Neuropathol Communen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1186/s40478-023-01563-4en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed37101235en_US
bordeaux.journalActa Neuropathologica Communicationsen_US
bordeaux.page68en_US
bordeaux.volume11en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamELEANORen_US
bordeaux.teamPHARESen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDNational Institutes of Healthen_US
bordeaux.identifier.funderIDChan Zuckerberg Initiativeen_US
bordeaux.identifier.funderIDMichael J. Fox Foundation for Parkinson's Researchen_US
bordeaux.identifier.funderIDGE Healthcareen_US
bordeaux.import.sourcepubmed
hal.identifierhal-04228529
hal.version1
hal.date.transferred2023-10-04T13:39:35Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccPas de Licence CCen_US
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