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New insights into the genetic etiology of Alzheimer's disease and related dementias

dc.contributor.authorBellenguez, C.
dc.contributor.authorKüçükali, F.
dc.contributor.authorJansen, I.E.
dc.contributor.authorKleineidam, L.
dc.contributor.authorMoreno-Grau, S.
dc.contributor.authorAmin, N.
dc.contributor.authorNaj, A.C.
dc.contributor.authorCampos-Martin, R.
dc.contributor.authorGrenier-Boley, B.
dc.contributor.authorAndrade, V.
dc.contributor.authorHolmans, P.A.
dc.contributor.authorBoland, A.
dc.contributor.authorDamotte, V.
dc.contributor.authorvan der Lee, S.J.
dc.contributor.authorCosta, M.R.
dc.contributor.authorKuulasmaa, T.
dc.contributor.authorYang, Q.
dc.contributor.authorde Rojas, I.
dc.contributor.authorBis, J.C.
dc.contributor.authorYaqub, A.
dc.contributor.authorProkic, I.
dc.contributor.authorChapuis, J.
dc.contributor.authorAhmad, S.
dc.contributor.authorGiedraitis, V.
dc.contributor.authorAarsland, D.
dc.contributor.authorGarcia-Gonzalez, P.
dc.contributor.authorAbdelnour, C.
dc.contributor.authorAlarcón-Martín, E.
dc.contributor.authorAlcolea, D.
dc.contributor.authorAlegret, M.
dc.contributor.authorAlvarez, I.
dc.contributor.authorÁlvarez, V.
dc.contributor.authorArmstrong, N.J.
dc.contributor.authorTsolaki, A.
dc.contributor.authorAntúnez, C.
dc.contributor.authorAppollonio, I.
dc.contributor.authorArcaro, M.
dc.contributor.authorArchetti, S.
dc.contributor.authorPastor, A.A.
dc.contributor.authorArosio, B.
dc.contributor.authorAthanasiu, L.
dc.contributor.authorBailly, H.
dc.contributor.authorBanaj, N.
dc.contributor.authorBaquero, M.
dc.contributor.authorBarral, S.
dc.contributor.authorBeiser, A.
dc.contributor.authorPastor, A.B.
dc.contributor.authorBelow, J.E.
dc.contributor.authorBenchek, P.
dc.contributor.authorBenussi, L.
dc.contributor.authorBerr, C.
dc.contributor.authorBesse, C.
dc.contributor.authorBessi, V.
dc.contributor.authorBinetti, G.
dc.contributor.authorBizarro, A.
dc.contributor.authorBlesa, R.
dc.contributor.authorBoada, M.
dc.contributor.authorBoerwinkle, E.
dc.contributor.authorBorroni, B.
dc.contributor.authorBoschi, S.
dc.contributor.authorBossù, P.
dc.contributor.authorBråthen, G.
dc.contributor.authorBressler, J.
dc.contributor.authorBresner, C.
dc.contributor.authorBrodaty, H.
dc.contributor.authorBrookes, K.J.
dc.contributor.authorBrusco, L.I.
dc.contributor.authorBuiza-Rueda, D.
dc.contributor.authorBûrger, K.
dc.contributor.authorBurholt, V.
dc.contributor.authorBush, W.S.
dc.contributor.authorCalero, M.
dc.contributor.authorCantwell, L.B.
dc.contributor.authorChene, G.
dc.contributor.authorChung, J.
dc.contributor.authorCuccaro, M.L.
dc.contributor.authorCarracedo Álvarez, Ángel
dc.contributor.authorCecchetti, R.
dc.contributor.authorCervera-Carles, L.
dc.contributor.authorCharbonnier, C.
dc.contributor.authorChen, H.-H.
dc.contributor.authorChillotti, C.
dc.contributor.authorCiccone, S.
dc.contributor.authorClaassen, J.A.H.R.
dc.contributor.authorClark, C.
dc.contributor.authorConti, E.
dc.contributor.authorCorma-Gómez, A.
dc.contributor.authorCostantini, E.
dc.contributor.authorCustodero, C.
dc.contributor.authorDaian, D.
dc.contributor.authorDalmasso, M.C.
dc.contributor.authorDaniele, A.
dc.contributor.authorDardiotis, E.
dc.contributor.authorDartigues, J.-F.
dc.contributor.authorde Deyn, P.P.
dc.contributor.authorde Paiva Lopes, K.
dc.contributor.authorde Witte, L.D.
dc.contributor.authorDebette, S.
dc.contributor.authorDeckert, J.
dc.contributor.authorDel Ser, T.
dc.contributor.authorDenning, N.
dc.contributor.authorDeStefano, A.
dc.contributor.authorDichgans, M.
dc.contributor.authorDiehl-Schmid, J.
dc.contributor.authorDiez-Fairen, M.
dc.contributor.authorRossi, P.D.
dc.contributor.authorDjurovic, S.
dc.contributor.authorDuron, E.
dc.contributor.authorDüzel, E.
dc.contributor.authorDufouil, C.
dc.contributor.authorEiriksdottir, G.
dc.contributor.authorEngelborghs, S.
dc.contributor.authorEscott-Price, V.
dc.contributor.authorEspinosa, A.
dc.contributor.authorEwers, M.
dc.contributor.authorFaber, K.M.
dc.contributor.authorFabrizio, T.
dc.contributor.authorNielsen, S.F.
dc.contributor.authorFardo, D.W.
dc.contributor.authorFarotti, L.
dc.contributor.authorFenoglio, C.
dc.contributor.authorFernández-Fuertes, M.
dc.contributor.authorFerrari, R.
dc.contributor.authorFerreira, C.B.
dc.contributor.authorFerri, E.
dc.contributor.authorFin, B.
dc.contributor.authorFischer, P.
dc.contributor.authorFladby, T.
dc.contributor.authorFließbach, K.
dc.contributor.authorFongang, B.
dc.contributor.authorFornage, M.
dc.contributor.authorFortea, J.
dc.contributor.authorForoud, T.M.
dc.contributor.authorFostinelli, S.
dc.contributor.authorFox, N.C.
dc.contributor.authorFranco-Macías, E.
dc.contributor.authorBullido, M.J.
dc.contributor.authorFrank-García, A.
dc.contributor.authorFroelich, L.
dc.contributor.authorFulton-Howard, B.
dc.contributor.authorGalimberti, D.
dc.contributor.authorGarcía-Alberca, J.M.
dc.contributor.authorGarcía-González, P.
dc.contributor.authorGarcia-Madrona, S.
dc.contributor.authorGarcia-Ribas, G.
dc.contributor.authorGhidoni, R.
dc.contributor.authorGiegling, I.
dc.contributor.authorGiorgio, G.
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dc.contributor.authorGraff, C.
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dc.contributor.authorHarwood, J.
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dc.contributor.authorHelisalmi, S.
dc.contributor.authorHeneka, M.T.
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dc.contributor.authorHerrmann, M.J.
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dc.contributor.authorKastumata, Y.
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dc.contributor.authorKilander, L.
dc.contributor.authorStåhlbom, A.K.
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dc.contributor.authorKoivisto, A.
dc.contributor.authorKornhuber, J.
dc.contributor.authorKosmidis, M.H.
dc.contributor.authorKukull, W.A.
dc.contributor.authorKuksa, P.P.
dc.contributor.authorKunkle, B.W.
dc.contributor.authorKuzma, A.B.
dc.contributor.authorLage, C.
dc.contributor.authorLaukka, E.J.
dc.contributor.authorLauner, L.
dc.contributor.authorLauria, A.
dc.contributor.authorLee, C.-Y.
dc.contributor.authorLehtisalo, J.
dc.contributor.authorLerch, O.
dc.contributor.authorLleó, A.
dc.contributor.authorLongstreth, W.
dc.contributor.authorLopez, O.
dc.contributor.authorde Munain, A.L.
dc.contributor.authorLove, S.
dc.contributor.authorLöwemark, M.
dc.contributor.authorLuckcuck, L.
dc.contributor.authorLunetta, K.L.
dc.contributor.authorMa, Y.
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dc.contributor.authorMarshall, R.
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dc.contributor.authorMir, P.
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dc.contributor.authorMoreno, F.
dc.contributor.authorMorgan, K.
dc.contributor.authorMosley, T.
dc.contributor.authorNöthen, M.M.
dc.contributor.authorMuchnik, C.
dc.contributor.authorMukherjee, S.
dc.contributor.authorNacmias, B.
dc.contributor.authorNgandu, T.
dc.contributor.authorNicolas, G.
dc.contributor.authorNordestgaard, B.G.
dc.contributor.authorOlaso, R.
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dc.contributor.authorPaolo, C.
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dc.contributor.authorQuintela García, Inés
dc.contributor.authorThomassen, J.Q.
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dc.contributor.authorRajabli, F.
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dc.contributor.authorRidge, P.
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dc.contributor.authorFarrer, L.A.
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dc.contributor.authorGhanbari, M.
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dc.contributor.authorSachdev, P.
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dc.contributor.authorJessen, F.
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dc.contributor.authorde Mendonça, A.
dc.contributor.authorHort, J.
dc.contributor.authorTsolaki, M.
dc.contributor.authorPericak-Vance, M.A.
dc.contributor.authorAmouyel, P.
dc.contributor.authorWilliams, J.
dc.contributor.authorFrikke-Schmidt, R.
dc.contributor.authorClarimon, J.
dc.contributor.authorDeleuze, J.-F.
dc.contributor.authorRossi, G.
dc.contributor.authorSeshadri, S.
dc.contributor.authorAndreassen, O.A.
dc.contributor.authorIngelsson, M.
dc.contributor.authorHiltunen, M.
dc.contributor.authorSleegers, K.
dc.contributor.authorSchellenberg, G.D.
dc.contributor.authorvan Duijn, C.M.
dc.contributor.authorSims, R.
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dc.contributor.authorLambert, J.-C.
dc.date.accessioned2025-08-25T12:43:23Z
dc.date.available2025-08-25T12:43:23Z
dc.date.issued2022
dc.identifier.citationBellenguez C, Küçükali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N, et al. New insights into the genetic etiology of Alzheimer's disease and related dementias. Nature genetics. 2022;54(4):412-36.
dc.identifier.issn1546-1718
dc.identifier.otherhttps://portalcientifico.sergas.gal/documentos/626d908d3541a83b39a1cb9e*
dc.identifier.urihttp://hdl.handle.net/20.500.11940/20514
dc.description.abstractCharacterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ?4 allele.en
dc.description.sponsorshipWe thank the many study participants, researchers and staff for collecting and contributing to the data, the high-performance computing service at the University of Lille and the staff at CEA-CNRGH for their help with sample preparation and genotyping and excellent technical assistance. We thank Antonio Pardinas for his help. We thank the Netherlands Brain Bank. This research was conducted using the UKBB resource (application number 61054). This work was funded by a grant (EADB) from the EU Joint Programme - Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Metropole Communaute Urbaine and French government's LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Note.en
dc.language.isoeng
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleNew insights into the genetic etiology of Alzheimer's disease and related dementias*
dc.typeArticleen
dc.authorsophosBellenguez, J. C. C.
dc.authorsophosKüçükali, F.
dc.authorsophosJansen, I. E.
dc.authorsophosKleineidam, L.
dc.authorsophosMoreno-Grau, S.
dc.authorsophosAmin, N.
dc.authorsophosNaj, A. C.
dc.authorsophosCampos-Martin, R.
dc.authorsophosGrenier-Boley, B.
dc.authorsophosAndrade, V.
dc.authorsophosHolmans, P. A.
dc.authorsophosBoland, A.
dc.authorsophosDamotte, V.
dc.authorsophosvan der Lee, S. J.
dc.authorsophosCosta, M. R.
dc.authorsophosKuulasmaa, T.
dc.authorsophosYang, Q.
dc.authorsophosde Rojas, I.
dc.authorsophosBis, J. C.
dc.authorsophosYaqub, A.
dc.authorsophosProkic, I.
dc.authorsophosChapuis, J.
dc.authorsophosAhmad, S.
dc.authorsophosGiedraitis, V.
dc.authorsophosAarsland, D.
dc.authorsophosGarcia-Gonzalez, P.
dc.authorsophosAbdelnour, C.
dc.authorsophosAlarcón-Martín, E.
dc.authorsophosAlcolea, D.
dc.authorsophosAlegret, M.
dc.authorsophosAlvarez, I.
dc.authorsophosÁlvarez, V.
dc.authorsophosArmstrong, N. J.
dc.authorsophosTsolaki, A.
dc.authorsophosAntúnez, C.
dc.authorsophosAppollonio, I.
dc.authorsophosArcaro, M.
dc.authorsophosArchetti, S.
dc.authorsophosPastor, A. A.
dc.authorsophosArosio, B.
dc.authorsophosAthanasiu, L.
dc.authorsophosBailly, H.
dc.authorsophosBanaj, N.
dc.authorsophosBaquero, M.
dc.authorsophosBarral, S.
dc.authorsophosBeiser, A.
dc.authorsophosPastor, A. B.
dc.authorsophosBelow, J. E.
dc.authorsophosBenchek, P.
dc.authorsophosBenussi, L.
dc.authorsophosBerr, C.
dc.authorsophosBesse, C.
dc.authorsophosBessi, V.
dc.authorsophosBinetti, G.
dc.authorsophosBizarro, A.
dc.authorsophosBlesa, R.
dc.authorsophosBoada, M.
dc.authorsophosBoerwinkle, E.
dc.authorsophosBorroni, B.
dc.authorsophosBoschi, S.
dc.authorsophosBossù, P.
dc.authorsophosBråthen, G.
dc.authorsophosBressler, J.
dc.authorsophosBresner, C.
dc.authorsophosBrodaty, H.
dc.authorsophosBrookes, K. J.
dc.authorsophosBrusco, L. I.
dc.authorsophosBuiza-Rueda, D.
dc.authorsophosBûrger, K.
dc.authorsophosBurholt, V.
dc.authorsophosBush, W. S.
dc.authorsophosCalero, M.
dc.authorsophosCantwell, L. B.
dc.authorsophosChene, G.
dc.authorsophosChung, J.
dc.authorsophosCuccaro, M. L.
dc.authorsophosCarracedo, Á
dc.authorsophosCecchetti, R.
dc.authorsophosCervera-Carles, L.
dc.authorsophosCharbonnier, C.
dc.authorsophosChen, H. H.
dc.authorsophosChillotti, C.
dc.authorsophosCiccone, S.
dc.authorsophosClaassen, J. A. H. R.
dc.authorsophosClark, C.
dc.authorsophosConti, E.
dc.authorsophosCorma-Gómez, A.
dc.authorsophosCostantini, E.
dc.authorsophosCustodero, C.
dc.authorsophosDaian, D.
dc.authorsophosDalmasso, M. C.
dc.authorsophosDaniele, A.
dc.authorsophosDardiotis, E.
dc.authorsophosDartigues, J. F.
dc.authorsophosde Deyn, P. P.
dc.authorsophosde Paiva Lopes, K.
dc.authorsophosde Witte, L. D.
dc.authorsophosDebette, S.
dc.authorsophosDeckert, J.
dc.authorsophosDel Ser, T.
dc.authorsophosDenning, N.
dc.authorsophosDeStefano, A.
dc.authorsophosDichgans, M.
dc.authorsophosDiehl-Schmid, J.
dc.authorsophosDiez-Fairen, M.
dc.authorsophosRossi, P. D.
dc.authorsophosDjurovic, S.
dc.authorsophosDuron, E.
dc.authorsophosDüzel, E.
dc.authorsophosDufouil, C.
dc.authorsophosEiriksdottir, G.
dc.authorsophosEngelborghs, S.
dc.authorsophosEscott-Price, V.
dc.authorsophosEspinosa, A.
dc.authorsophosEwers, M.
dc.authorsophosFaber, K. M.
dc.authorsophosFabrizio, T.
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dc.authorsophosLambert
dc.identifier.doi10.1038/s41588-022-01024-z
dc.identifier.sophos626d908d3541a83b39a1cb9e
dc.issue.number4
dc.journal.titleNature genetics*
dc.page.initial412
dc.page.final436
dc.relation.projectIDEU Joint Programme - Neurodegenerative Disease Research; INSERM; Institut Pasteur de Lille; Lille Metropole Communaute Urbaine; French government's LABEX DISTALZ program; Medical Research Council [G0902227, MR/L023784/1, MR/L010305/1, MR/N029402/1, UKDRI-1009, MR/R024804/1, MR/L501517/1, MR/L023784/2, G0300429, G0701075, G0601022, MR/K013041/1, UKDRI-3003, G9901400, G0901254, MC_PC_17112, MR/L501529/1, UKDRI-2002, UKDRI-1001] Funding Source: researchfish; Motor Neurone Disease Association [AlChalabi-Dobson/Apr14/829-791] Funding Source: researchfish; National Institute for Health Research [NIHR202421] Funding Source: researchfish; National Human Genome Research Institute [U01HG008657] Funding Source: NIH RePORTER; National Institute on Aging [R01AG015819, K99AG066849, R01AG062622, U01AG046139, U24AG041689, R01AG054005, R01AG017917, U01AG058654, U01AG061356, F99AG073565, P01AG019724, P30AG062422, R01AG022018, U01AG068880] Funding Source: NIH RePORTER; MRC [MR/T04604X/1, MR/R024804/1, MR/K013041/1, MR/L501517/1, MR/L501529/1, MC_PC_17112, MR/L023784/1, MR/L023784/2, MR/N029402/1] Funding Source: UKRI
dc.relation.publisherversionhttps://www.nature.com/articles/s41588-022-01024-z.pdfes
dc.rights.accessRightsopenAccess
dc.subject.keywordFPGMXes
dc.subject.keywordAS Santiagoes
dc.subject.keywordIDISes
dc.typefidesArtículo Científico (incluye Original, Original breve, Revisión Sistemática y Meta-análisis)es
dc.typesophosArtículo Originales
dc.volume.number54


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