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Whole exome sequencing study identifies novel rare and common Alzheimer's-Associated variants involved in immune response and transcriptional regulation

dc.rights.licenseopenen_US
dc.contributor.authorBIS, J. C.
dc.contributor.authorJIAN, X.
dc.contributor.authorKUNKLE, B. W.
dc.contributor.authorCHEN, Y.
dc.contributor.authorHAMILTON-NELSON, K. L.
dc.contributor.authorBUSH, W. S.
dc.contributor.authorSALERNO, W. J.
dc.contributor.authorLANCOUR, D.
dc.contributor.authorMA, Y.
dc.contributor.authorRENTON, A. E.
dc.contributor.authorMARCORA, E.
dc.contributor.authorFARRELL, J. J.
dc.contributor.authorZHAO, Y.
dc.contributor.authorQU, L.
dc.contributor.authorAHMAD, S.
dc.contributor.authorAMIN, N.
dc.contributor.authorAMOUYEL, Philippe
dc.contributor.authorBEECHAM, G. W.
dc.contributor.authorBELOW, J. E.
dc.contributor.authorCAMPION, D.
dc.contributor.authorCANTWELL, L.
dc.contributor.authorCHARBONNIER, C.
dc.contributor.authorCHUNG, J.
dc.contributor.authorCRANE, P. K.
dc.contributor.authorCRUCHAGA, C.
dc.contributor.authorCUPPLES, L. A.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDARTIGUES, Jean-Francois
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorDELEUZE, J. F.
dc.contributor.authorFULTON, L.
dc.contributor.authorGABRIEL, S. B.
dc.contributor.authorGENIN, E.
dc.contributor.authorGIBBS, R. A.
dc.contributor.authorGOATE, A.
dc.contributor.authorGRENIER-BOLEY, B.
dc.contributor.authorGUPTA, N.
dc.contributor.authorHAINES, J. L.
dc.contributor.authorHAVULINNA, A. S.
dc.contributor.authorHELISALMI, S.
dc.contributor.authorHILTUNEN, M.
dc.contributor.authorHOWRIGAN, D. P.
dc.contributor.authorIKRAM, M. A.
dc.contributor.authorKAPRIO, J.
dc.contributor.authorKONRAD, J.
dc.contributor.authorKUZMA, A.
dc.contributor.authorLANDER, E. S.
dc.contributor.authorLATHROP, M.
dc.contributor.authorLEHTIMAKI, T.
dc.contributor.authorLIN, H.
dc.contributor.authorMATTILA, K.
dc.contributor.authorMAYEUX, R.
dc.contributor.authorMUZNY, D. M.
dc.contributor.authorNASSER, W.
dc.contributor.authorNEALE, B.
dc.contributor.authorNHO, K.
dc.contributor.authorNICOLAS, G.
dc.contributor.authorPATEL, D.
dc.contributor.authorPERICAK-VANCE, M. A.
dc.contributor.authorPEROLA, M.
dc.contributor.authorPSATY, B. M.
dc.contributor.authorQUENEZ, O.
dc.contributor.authorRAJABLI, F.
dc.contributor.authorREDON, R.
dc.contributor.authorREITZ, C.
dc.contributor.authorREMES, A. M.
dc.contributor.authorSALOMAA, V.
dc.contributor.authorSARNOWSKI, C.
dc.contributor.authorSCHMIDT, H.
dc.contributor.authorSCHMIDT, M.
dc.contributor.authorSCHMIDT, R.
dc.contributor.authorSOININEN, H.
dc.contributor.authorTHORNTON, T. A.
dc.contributor.authorTOSTO, G.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTZOURIO, Christophe
dc.contributor.authorVAN DER LEE, S. J.
dc.contributor.authorVAN DUIJN, C. M.
dc.contributor.authorVALLADARES, O.
dc.contributor.authorVARDARAJAN, B.
dc.contributor.authorWANG, L. S.
dc.contributor.authorWANG, W.
dc.contributor.authorWIJSMAN, E.
dc.contributor.authorWILSON, R. K.
dc.contributor.authorWITTEN, D.
dc.contributor.authorWORLEY, K. C.
dc.contributor.authorZHANG, X.
dc.contributor.authorBELLENGUEZ, C.
dc.contributor.authorLAMBERT, J. C.
dc.contributor.authorKURKI, M. I.
dc.contributor.authorPALOTIE, A.
dc.contributor.authorDALY, M.
dc.contributor.authorBOERWINKLE, E.
dc.contributor.authorLUNETTA, K. L.
dc.contributor.authorDESTEFANO, A. L.
dc.contributor.authorDUPUIS, J.
dc.contributor.authorMARTIN, E. R.
dc.contributor.authorSCHELLENBERG, G. D.
dc.contributor.authorSESHADRI, Sudha
dc.contributor.authorNAJ, A. C.
dc.contributor.authorFORNAGE, M.
dc.contributor.authorFARRER, L. A.
dc.date.accessioned2021-03-23T09:30:12Z
dc.date.available2021-03-23T09:30:12Z
dc.date.issued2020-08
dc.identifier.issn1476-5578 (Electronic) 1359-4184 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26787
dc.description.abstractEnThe Alzheimer's Disease Sequencing Project (ADSP) undertook whole exome sequencing in 5,740 late-onset Alzheimer disease (AD) cases and 5,096 cognitively normal controls primarily of European ancestry (EA), among whom 218 cases and 177 controls were Caribbean Hispanic (CH). An age-, sex- and APOE based risk score and family history were used to select cases most likely to harbor novel AD risk variants and controls least likely to develop AD by age 85 years. We tested ~1.5 million single nucleotide variants (SNVs) and 50,000 insertion-deletion polymorphisms (indels) for association to AD, using multiple models considering individual variants as well as gene-based tests aggregating rare, predicted functional, and loss of function variants. Sixteen single variants and 19 genes that met criteria for significant or suggestive associations after multiple-testing correction were evaluated for replication in four independent samples; three with whole exome sequencing (2,778 cases, 7,262 controls) and one with genome-wide genotyping imputed to the Haplotype Reference Consortium panel (9,343 cases, 11,527 controls). The top findings in the discovery sample were also followed-up in the ADSP whole-genome sequenced family-based dataset (197 members of 42 EA families and 501 members of 157 CH families). We identified novel and predicted functional genetic variants in genes previously associated with AD. We also detected associations in three novel genes: IGHG3 (p = 9.8 x 10(-7)), an immunoglobulin gene whose antibodies interact with beta-amyloid, a long non-coding RNA AC099552.4 (p = 1.2 x 10(-7)), and a zinc-finger protein ZNF655 (gene-based p = 5.0 x 10(-6)). The latter two suggest an important role for transcriptional regulation in AD pathogenesis.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enWhole exome sequencing study identifies novel rare and common Alzheimer's-Associated variants involved in immune response and transcriptional regulation
dc.title.alternativeMol Psychiatryen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41380-018-0112-7en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed30108311en_US
bordeaux.journalMolecular Psychiatryen_US
bordeaux.page1859-1875en_US
bordeaux.volume25en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue8en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamSEPIAen_US
bordeaux.teamVINTAGEen_US
bordeaux.teamHEALTHY_BPH
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03177410
hal.version1
hal.date.transferred2021-03-23T09:30:23Z
hal.exporttrue
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