dc.rights.license | open | en_US |
dc.contributor.author | ALI, Muhammad | |
dc.contributor.author | ARCHER, Derek B | |
dc.contributor.author | GORIJALA, Priyanka | |
dc.contributor.author | WESTERN, Daniel | |
dc.contributor.author | TIMSINA, Jigyasha | |
dc.contributor.author | FERNÁNDEZ, Maria V | |
dc.contributor.author | WANG, Ting-Chen | |
dc.contributor.author | SATIZABAL, Claudia L | |
dc.contributor.author | YANG, Qiong | |
dc.contributor.author | BEISER, Alexa S | |
dc.contributor.author | WANG, Ruiqi | |
dc.contributor.author | CHEN, Gengsheng | |
dc.contributor.author | GORDON, Brian | |
dc.contributor.author | BENZINGER, Tammie L S | |
dc.contributor.author | XIONG, Chengjie | |
dc.contributor.author | MORRIS, John C | |
dc.contributor.author | BATEMAN, Randall J | |
dc.contributor.author | KARCH, Celeste M | |
dc.contributor.author | MCDADE, Eric | |
dc.contributor.author | GOATE, Alison | |
dc.contributor.author | SESHADRI, Sudha | |
dc.contributor.author | MAYEUX, Richard P | |
dc.contributor.author | SPERLING, Reisa A | |
dc.contributor.author | BUCKLEY, Rachel F | |
dc.contributor.author | JOHNSON, Keith A | |
dc.contributor.author | WON, Hong-Hee | |
dc.contributor.author | JUNG, Sang-Hyuk | |
dc.contributor.author | KIM, Hang-Rai | |
dc.contributor.author | SEO, Sang Won | |
dc.contributor.author | KIM, Hee Jin | |
dc.contributor.author | MORMINO, Elizabeth | |
dc.contributor.author | LAWS, Simon M | |
dc.contributor.author | FAN, Kang-Hsien | |
dc.contributor.author | KAMBOH, M Ilyas | |
dc.contributor.author | VEMURI, Prashanthi | |
dc.contributor.author | RAMANAN, Vijay K | |
dc.contributor.author | YANG, Hyun-Sik | |
dc.contributor.author | WENZEL, Allen | |
hal.structure.identifier | Bordeaux population health [BPH] | |
dc.contributor.author | RAJULA, Hema Sekhar Reddy | |
hal.structure.identifier | Bordeaux population health [BPH] | |
dc.contributor.author | MISHRA, Aniket | |
hal.structure.identifier | Bordeaux population health [BPH] | |
dc.contributor.author | DUFOUIL, Carole | |
hal.structure.identifier | Bordeaux population health [BPH] | |
dc.contributor.author | DEBETTE, Stephanie | |
dc.contributor.author | LOPEZ, Oscar L | |
dc.contributor.author | DEKOSKY, Steven T | |
dc.contributor.author | TAO, Feifei | |
dc.contributor.author | NAGLE, Michael W | |
dc.contributor.author | HOHMAN, Timothy J | |
dc.contributor.author | SUNG, Yun Ju | |
dc.contributor.author | DUMITRESCU, Logan | |
dc.contributor.author | CRUCHAGA, Carlos | |
dc.date.accessioned | 2023-10-04T13:39:26Z | |
dc.date.available | 2023-10-04T13:39:26Z | |
dc.date.issued | 2023-04-26 | |
dc.identifier.issn | 2051-5960 | en_US |
dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/184317 | |
dc.description.abstractEn | Amyloid 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.iso | EN | en_US |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.subject.en | Humans | |
dc.subject.en | Female | |
dc.subject.en | Alzheimer Disease | |
dc.subject.en | Amyloid beta-Peptides | |
dc.subject.en | Genome-Wide Association Study | |
dc.subject.en | Amyloidosis | |
dc.subject.en | Amyloid | |
dc.subject.en | Apolipoproteins E | |
dc.title.en | Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease. | |
dc.title.alternative | Acta Neuropathol Commun | en_US |
dc.type | Article de revue | en_US |
dc.identifier.doi | 10.1186/s40478-023-01563-4 | en_US |
dc.subject.hal | Sciences du Vivant [q-bio]/Santé publique et épidémiologie | en_US |
dc.identifier.pubmed | 37101235 | en_US |
bordeaux.journal | Acta Neuropathologica Communications | en_US |
bordeaux.page | 68 | en_US |
bordeaux.volume | 11 | en_US |
bordeaux.hal.laboratories | Bordeaux Population Health Research Center (BPH) - UMR 1219 | en_US |
bordeaux.issue | 1 | en_US |
bordeaux.institution | Université de Bordeaux | en_US |
bordeaux.institution | INSERM | en_US |
bordeaux.team | ELEANOR | en_US |
bordeaux.team | PHARES | en_US |
bordeaux.peerReviewed | oui | en_US |
bordeaux.inpress | non | en_US |
bordeaux.identifier.funderID | National Institutes of Health | en_US |
bordeaux.identifier.funderID | Chan Zuckerberg Initiative | en_US |
bordeaux.identifier.funderID | Michael J. Fox Foundation for Parkinson's Research | en_US |
bordeaux.identifier.funderID | GE Healthcare | en_US |
bordeaux.import.source | pubmed | |
hal.identifier | hal-04228529 | |
hal.version | 1 | |
hal.date.transferred | 2023-10-04T13:39:35Z | |
hal.popular | non | en_US |
hal.audience | Internationale | en_US |
hal.export | true | |
workflow.import.source | pubmed | |
dc.rights.cc | Pas de Licence CC | en_US |
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