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Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing

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dc.contributor.authorKUNKLE, B. W.
dc.contributor.authorGRENIER-BOLEY, B.
dc.contributor.authorSIMS, R.
dc.contributor.authorBIS, J. C.
dc.contributor.authorDAMOTTE, V.
dc.contributor.authorNAJ, A. C.
dc.contributor.authorBOLAND, A.
dc.contributor.authorVRONSKAYA, M.
dc.contributor.authorVAN DER LEE, S. J.
dc.contributor.authorAMLIE-WOLF, A.
dc.contributor.authorBELLENGUEZ, C.
dc.contributor.authorFRIZATTI, A.
dc.contributor.authorCHOURAKI, V.
dc.contributor.authorMARTIN, E. R.
dc.contributor.authorSLEEGERS, K.
dc.contributor.authorBADARINARAYAN, N.
dc.contributor.authorJAKOBSDOTTIR, J.
dc.contributor.authorHAMILTON-NELSON, K. L.
dc.contributor.authorMORENO-GRAU, S.
dc.contributor.authorOLASO, R.
dc.contributor.authorRAYBOULD, R.
dc.contributor.authorCHEN, Y.
dc.contributor.authorKUZMA, A. B.
dc.contributor.authorHILTUNEN, M.
dc.contributor.authorMORGAN, T.
dc.contributor.authorAHMAD, S.
dc.contributor.authorVARDARAJAN, B. N.
dc.contributor.authorEPELBAUM, J.
dc.contributor.authorHOFFMANN, P.
dc.contributor.authorBOADA, M.
dc.contributor.authorBEECHAM, G. W.
dc.contributor.authorGARNIER, J. G.
dc.contributor.authorHAROLD, D.
dc.contributor.authorFITZPATRICK, A. L.
dc.contributor.authorVALLADARES, O.
dc.contributor.authorMOUTET, M. L.
dc.contributor.authorGERRISH, A.
dc.contributor.authorSMITH, A. V.
dc.contributor.authorQU, L.
dc.contributor.authorBACQ, D.
dc.contributor.authorDENNING, N.
dc.contributor.authorJIAN, X.
dc.contributor.authorZHAO, Y.
dc.contributor.authorDEL ZOMPO, M.
dc.contributor.authorFOX, N. C.
dc.contributor.authorCHOI, S. H.
dc.contributor.authorMATEO, I.
dc.contributor.authorHUGHES, J. T.
dc.contributor.authorADAMS, H. H.
dc.contributor.authorMALAMON, J.
dc.contributor.authorSANCHEZ-GARCIA, F.
dc.contributor.authorPATEL, Y.
dc.contributor.authorBRODY, J. A.
dc.contributor.authorDOMBROSKI, B. A.
dc.contributor.authorNARANJO, M. C. D.
dc.contributor.authorDANIILIDOU, M.
dc.contributor.authorEIRIKSDOTTIR, G.
dc.contributor.authorMUKHERJEE, S.
dc.contributor.authorWALLON, D.
dc.contributor.authorUPHILL, J.
dc.contributor.authorASPELUND, T.
dc.contributor.authorCANTWELL, L. B.
dc.contributor.authorGARZIA, F.
dc.contributor.authorGALIMBERTI, D.
dc.contributor.authorHOFER, E.
dc.contributor.authorBUTKIEWICZ, M.
dc.contributor.authorFIN, B.
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dc.contributor.authorSARNOWSKI, C.
dc.contributor.authorBUSH, W. S.
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dc.contributor.authorKORNHUBER, J.
dc.contributor.authorWHITE, C. C.
dc.contributor.authorSONG, Y.
dc.contributor.authorBARBER, R. C.
dc.contributor.authorENGELBORGHS, S.
dc.contributor.authorSORDON, S.
dc.contributor.authorVOIJNOVIC, D.
dc.contributor.authorADAMS, P. M.
dc.contributor.authorVANDENBERGHE, R.
dc.contributor.authorMAYHAUS, M.
dc.contributor.authorCUPPLES, L. A.
dc.contributor.authorALBERT, M. S.
dc.contributor.authorDE DEYN, P. P.
dc.contributor.authorGU, W.
dc.contributor.authorHIMALI, J. J.
dc.contributor.authorBEEKLY, D.
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dc.contributor.authorLIN, H.
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dc.contributor.authorMAIER, W.
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dc.contributor.authorCRIBBS, D. H.
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dc.contributor.authorRYAN, N. S.
dc.contributor.authorPOON, W. W.
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dc.contributor.authorCLARKE, R.
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dc.contributor.authorSMITH, A. D.
dc.contributor.authorRINGMAN, J. M.
dc.contributor.authorWARDEN, D.
dc.contributor.authorROBERSON, E. D.
dc.contributor.authorWILCOCK, G.
dc.contributor.authorROGAEVA, E.
dc.contributor.authorBRUNI, A. C.
dc.contributor.authorROSEN, H. J.
dc.contributor.authorGALLO, M.
dc.contributor.authorROSENBERG, R. N.
dc.contributor.authorBEN-SHLOMO, Y.
dc.contributor.authorSAGER, M. A.
dc.contributor.authorMECOCCI, P.
dc.contributor.authorSAYKIN, A. J.
dc.contributor.authorPASTOR, P.
dc.contributor.authorCUCCARO, M. L.
dc.contributor.authorVANCE, J. M.
dc.contributor.authorSCHNEIDER, J. A.
dc.contributor.authorSCHNEIDER, L. S.
dc.contributor.authorSLIFER, S.
dc.contributor.authorSEELEY, W. W.
dc.contributor.authorSMITH, A. G.
dc.contributor.authorSONNEN, J. A.
dc.contributor.authorSPINA, S.
dc.contributor.authorSTERN, R. A.
dc.contributor.authorSWERDLOW, R. H.
dc.contributor.authorTANG, M.
dc.contributor.authorTANZI, R. E.
dc.contributor.authorTROJANOWSKI, J. Q.
dc.contributor.authorTRONCOSO, J. C.
dc.contributor.authorVAN DEERLIN, V. M.
dc.contributor.authorVAN ELDIK, L. J.
dc.contributor.authorVINTERS, H. V.
dc.contributor.authorVONSATTEL, J. P.
dc.contributor.authorWEINTRAUB, S.
dc.contributor.authorWELSH-BOHMER, K. A.
dc.contributor.authorWILHELMSEN, K. C.
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dc.contributor.authorSABA, Y.
dc.contributor.authorALZHEIMER DISEASE GENETICS, Consortium
dc.contributor.authorEUROPEAN ALZHEIMER'S DISEASE, Initiative
dc.contributor.authorCOHORTS FOR, Heart
dc.contributor.authorAGING RESEARCH IN GENOMIC EPIDEMIOLOGY, Consortium
dc.contributor.authorGENETIC ENVIRONMENTAL RISK IN AD/DEFINING GENETIC, Polygenic
dc.contributor.authorENVIRONMENTAL RISK FOR ALZHEIMER'S DISEASE, Consortium
dc.contributor.authorPILOTTO, A.
dc.contributor.authorBULLIDO, M. J.
dc.contributor.authorPETERS, O.
dc.contributor.authorCRANE, P. K.
dc.contributor.authorBENNETT, D.
dc.contributor.authorBOSCO, P.
dc.contributor.authorCOTO, E.
dc.contributor.authorBOCCARDI, V.
dc.contributor.authorDE JAGER, P. L.
dc.contributor.authorLLEO, A.
dc.contributor.authorWARNER, N.
dc.contributor.authorLOPEZ, O. L.
dc.contributor.authorINGELSSON, M.
dc.contributor.authorDELOUKAS, P.
dc.contributor.authorCRUCHAGA, C.
dc.contributor.authorGRAFF, C.
dc.contributor.authorGWILLIAM, R.
dc.contributor.authorFORNAGE, M.
dc.contributor.authorGOATE, A. M.
dc.contributor.authorSANCHEZ-JUAN, P.
dc.contributor.authorKEHOE, P. G.
dc.contributor.authorAMIN, N.
dc.contributor.authorERTEKIN-TANER, N.
dc.contributor.authorBERR, C.
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorLOVE, S.
dc.contributor.authorLAUNER, L. J.
dc.contributor.authorYOUNKIN, S. G.
dc.contributor.authorDARTIGUES, Jean-Francois
dc.contributor.authorCORCORAN, C.
dc.contributor.authorIKRAM, M. A.
dc.contributor.authorDICKSON, D. W.
dc.contributor.authorNICOLAS, G.
dc.contributor.authorCAMPION, D.
dc.contributor.authorTSCHANZ, J.
dc.contributor.authorSCHMIDT, H.
dc.contributor.authorHAKONARSON, H.
dc.contributor.authorCLARIMON, J.
dc.contributor.authorMUNGER, R.
dc.contributor.authorSCHMIDT, R.
dc.contributor.authorFARRER, L. A.
dc.contributor.authorVAN BROECKHOVEN, C.
dc.contributor.authorM, C. O' Donovan
dc.contributor.authorDESTEFANO, A. L.
dc.contributor.authorJONES, L.
dc.contributor.authorHAINES, J. L.
dc.contributor.authorDELEUZE, J. F.
dc.contributor.authorOWEN, M. J.
dc.contributor.authorGUDNASON, V.
dc.contributor.authorMAYEUX, R.
dc.contributor.authorESCOTT-PRICE, V.
dc.contributor.authorPSATY, B. M.
dc.contributor.authorRAMIREZ, A.
dc.contributor.authorWANG, L. S.
dc.contributor.authorRUIZ, A.
dc.contributor.authorVAN DUIJN, C. M.
dc.contributor.authorHOLMANS, P. A.
dc.contributor.authorSESHADRI, Sudha
dc.contributor.authorWILLIAMS, J.
dc.contributor.authorAMOUYEL, Philippe
dc.contributor.authorSCHELLENBERG, G. D.
dc.contributor.authorLAMBERT, J. C.
dc.contributor.authorPERICAK-VANCE, M. A.
dc.date.accessioned2020-07-09T15:08:32Z
dc.date.available2020-07-09T15:08:32Z
dc.date.issued2019-03
dc.identifier.issn1546-1718 (Electronic) 1061-4036 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/10373
dc.description.abstractEnRisk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Abeta processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 x 10(-7)), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
dc.language.isoENen_US
dc.subject.enSEPIA
dc.subject.enFR
dc.subject.enVINTAGE
dc.title.enGenetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing
dc.title.alternativeNat Geneten_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41588-019-0358-2en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed30820047en_US
bordeaux.journalNature Geneticsen_US
bordeaux.page414-430en_US
bordeaux.volume51en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue3en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03209563
hal.version1
hal.date.transferred2021-04-28T01:51:14Z
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