Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease
dc.rights.license | open | en_US |
dc.contributor.author | HOLSTEGE, Henne | |
dc.contributor.author | HULSMAN, Marc | |
dc.contributor.author | CHARBONNIER, Camille | |
dc.contributor.author | GRENIER-BOLEY, Benjamin | |
dc.contributor.author | QUENEZ, Olivier | |
dc.contributor.author | GROZEVA, Detelina | |
dc.contributor.author | VAN ROOIJ, Jeroen G. J. | |
dc.contributor.author | SIMS, Rebecca | |
dc.contributor.author | AHMAD, Shahzad | |
dc.contributor.author | AMIN, Najaf | |
dc.contributor.author | NORSWORTHY, Penny J. | |
dc.contributor.author | DOLS-ICARDO, Oriol | |
dc.contributor.author | HUMMERICH, Holger | |
dc.contributor.author | KAWALIA, Amit | |
dc.contributor.author | AMOUYEL, Philippe | |
dc.contributor.author | BEECHAM, Gary W. | |
dc.contributor.author | BERR, Claudine | |
dc.contributor.author | BIS, Joshua C. | |
dc.contributor.author | BOLAND, Anne | |
dc.contributor.author | BOSSÙ, Paola | |
dc.contributor.author | BOUWMAN, Femke | |
dc.contributor.author | BRAS, Jose | |
dc.contributor.author | CAMPION, Dominique | |
dc.contributor.author | COCHRAN, J. Nicholas | |
dc.contributor.author | DANIELE, Antonio | |
hal.structure.identifier | Bordeaux population health [BPH] | |
dc.contributor.author | DARTIGUES, Jean-Francois | |
hal.structure.identifier | Bordeaux population health [BPH] | |
dc.contributor.author | DEBETTE, Stephanie | |
dc.contributor.author | DELEUZE, Jean-Francois | |
dc.contributor.author | DENNING, Nicola | |
dc.contributor.author | DESTEFANO, Anita L. | |
dc.contributor.author | FARRER, Lindsay A. | |
dc.contributor.author | FERNANDEZ, Maria Victoria | |
dc.contributor.author | FOX, Nick C. | |
dc.contributor.author | GALIMBERTI, Daniela | |
dc.contributor.author | GENIN, Emmanuelle | |
dc.contributor.author | GILLE, Johan J. P. | |
dc.contributor.author | LE GUEN, Yann | |
dc.contributor.author | GUERREIRO, Rita | |
dc.contributor.author | HAINES, Jonathan L. | |
dc.contributor.author | HOLMES, Clive | |
dc.contributor.author | IKRAM, M. Arfan | |
dc.contributor.author | IKRAM, M. Kamran | |
dc.contributor.author | JANSEN, Iris E. | |
dc.contributor.author | KRAAIJ, Robert | |
dc.contributor.author | LATHROP, Marc | |
dc.contributor.author | LEMSTRA, Afina W. | |
dc.contributor.author | LLEO, Alberto | |
dc.contributor.author | LUCKCUCK, Lauren | |
dc.contributor.author | MANNENS, Marcel M. A. M. | |
dc.contributor.author | MARSHALL, Rachel | |
dc.contributor.author | MARTIN, Eden R. | |
dc.contributor.author | MASULLO, Carlo | |
dc.contributor.author | MAYEUX, Richard | |
dc.contributor.author | MECOCCI, Patrizia | |
dc.contributor.author | MEGGY, Alun | |
dc.contributor.author | MOL, Merel O. | |
dc.contributor.author | MORGAN, Kevin | |
dc.contributor.author | MYERS, Richard M. | |
dc.contributor.author | NACMIAS, Benedetta | |
dc.contributor.author | NAJ, Adam C. | |
dc.contributor.author | NAPOLIONI, Valerio | |
dc.contributor.author | PASQUIER, Florence | |
dc.contributor.author | PASTOR, Pau | |
dc.contributor.author | PERICAK-VANCE, Margaret A. | |
dc.contributor.author | RAYBOULD, Rachel | |
dc.contributor.author | REDON, Richard | |
dc.contributor.author | REINDERS, Marcel J. T. | |
dc.contributor.author | RICHARD, Anne-Claire | |
dc.contributor.author | RIEDEL-HELLER, Steffi G. | |
dc.contributor.author | RIVADENEIRA, Fernando | |
dc.contributor.author | ROUSSEAU, Stephane | |
dc.contributor.author | RYAN, Natalie S. | |
dc.contributor.author | SAAD, Salha | |
dc.contributor.author | SANCHEZ-JUAN, Pascual | |
dc.contributor.author | SCHELLENBERG, Gerard D. | |
dc.contributor.author | SCHELTENS, Philip | |
dc.contributor.author | SCHOTT, Jonathan M. | |
dc.contributor.author | SERIPA, Davide | |
dc.contributor.author | SESHADRI, Sudha | |
dc.contributor.author | SIE, Daoud | |
dc.contributor.author | SISTERMANS, Erik A. | |
dc.contributor.author | SORBI, Sandro | |
dc.contributor.author | VAN SPAENDONK, Resie | |
dc.contributor.author | SPALLETTA, Gianfranco | |
dc.contributor.author | TESI, Niccolo’ | |
dc.contributor.author | TIJMS, Betty | |
dc.contributor.author | UITTERLINDEN, Andre G. | |
dc.contributor.author | VAN DER LEE, Sven J. | |
dc.contributor.author | VISSER, Pieter Jelle | |
dc.contributor.author | WAGNER, Michael | |
dc.contributor.author | WALLON, David | |
dc.contributor.author | WANG, Li-San | |
dc.contributor.author | ZAREA, Aline | |
dc.contributor.author | CLARIMON, Jordi | |
dc.contributor.author | VAN SWIETEN, John C. | |
dc.contributor.author | GREICIUS, Michael D. | |
dc.contributor.author | YOKOYAMA, Jennifer S. | |
dc.contributor.author | CRUCHAGA, Carlos | |
dc.contributor.author | HARDY, John | |
dc.contributor.author | RAMIREZ, Alfredo | |
dc.contributor.author | MEAD, Simon | |
dc.contributor.author | VAN DER FLIER, Wiesje M. | |
dc.contributor.author | VAN DUIJN, Cornelia M. | |
dc.contributor.author | WILLIAMS, Julie | |
dc.contributor.author | NICOLAS, Gael | |
dc.contributor.author | BELLENGUEZ, Celine | |
dc.contributor.author | LAMBERT, Jean-Charles | |
dc.date.accessioned | 2022-12-15T11:00:54Z | |
dc.date.available | 2022-12-15T11:00:54Z | |
dc.date.issued | 2022-11-21 | |
dc.identifier.issn | 1546-1718 (Electronic) 1061-4036 (Linking) | en_US |
dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/171539 | |
dc.description.abstractEn | Alzheimer'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.iso | EN | en_US |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.title.en | Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease | |
dc.type | Article de revue | en_US |
dc.identifier.doi | 10.1038/s41588-022-01208-7 | en_US |
dc.subject.hal | Sciences du Vivant [q-bio]/Santé publique et épidémiologie | en_US |
dc.identifier.pubmed | 36411364 | en_US |
bordeaux.journal | Nature Genetics | en_US |
bordeaux.page | 1786-1794 | en_US |
bordeaux.volume | 54 | en_US |
bordeaux.hal.laboratories | Bordeaux Population Health Research Center (BPH) - UMR 1219 | en_US |
bordeaux.institution | Université de Bordeaux | en_US |
bordeaux.institution | INSERM | en_US |
bordeaux.team | ACTIVE_BPH | en_US |
bordeaux.team | ELEANOR_BPH | en_US |
bordeaux.peerReviewed | oui | en_US |
bordeaux.inpress | non | en_US |
hal.identifier | hal-03900692 | |
hal.version | 1 | |
hal.date.transferred | 2022-12-15T11:01:25Z | |
hal.export | true | |
dc.rights.cc | Pas de Licence CC | en_US |
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