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dc.contributor.authorde Rojas, Itziar
dc.contributor.authorMoreno-Grau, Sonia
dc.contributor.authorTesi, Niccolo
dc.contributor.authorGrenier-Boley, Benjamin
dc.contributor.authorAndrade, Victor
dc.contributor.authorJansen, Iris E
dc.contributor.authorPedersen, Nancy L
dc.contributor.authorStringa, Najada
dc.contributor.authorZettergren, Anna
dc.contributor.authorHernández, Isabel
dc.contributor.authorMontrreal, Laura
dc.contributor.authorAntúnez, Carmen
dc.contributor.authorAntonell, Anna
dc.contributor.authorTankard, Rick M
dc.contributor.authorBis, Joshua C
dc.contributor.authorSims, Rebecca
dc.contributor.authorBellenguez, Céline
dc.contributor.authorQuintela, Inés
dc.contributor.authorGonzález-Perez, Antonio
dc.contributor.authorCalero, Miguel 
dc.contributor.authorFranco-Macías, Emilio
dc.contributor.authorMacías, Juan
dc.contributor.authorBlesa, Rafael
dc.contributor.authorCervera-Carles, Laura
dc.contributor.authorMenéndez-González, Manuel
dc.contributor.authorFrank-García, Ana
dc.contributor.authorRoyo, Jose Luís
dc.contributor.authorMoreno, Fermin
dc.contributor.authorHuerto Vilas, Raquel
dc.contributor.authorBaquero, Miquel
dc.contributor.authorDiez-Fairen, Mónica
dc.contributor.authorLage, Carmen
dc.contributor.authorGarcía-Madrona, Sebastián
dc.contributor.authorGarcía-González, Pablo
dc.contributor.authorAlarcón-Martín, Emilio
dc.contributor.authorValero, Sergi
dc.contributor.authorSotolongo-Grau, Oscar
dc.contributor.authorUllgren, Abbe
dc.contributor.authorNaj, Adam C
dc.contributor.authorLemstra, Afina W
dc.contributor.authorBenaque, Alba
dc.contributor.authorPérez-Cordón, Alba
dc.contributor.authorBenussi, Alberto
dc.contributor.authorRábano, Alberto
dc.contributor.authorPadovani, Alessandro
dc.contributor.authorSquassina, Alessio
dc.contributor.authorde Mendonça, Alexandre
dc.contributor.authorArias Pastor, Alfonso
dc.contributor.authorKok, Almar A L
dc.contributor.authorMeggy, Alun
dc.contributor.authorPastor, Ana Belén
dc.contributor.authorEspinosa, Ana
dc.contributor.authorCorma-Gómez, Anaïs
dc.contributor.authorMartín Montes, Angel
dc.contributor.authorSanabria, Ángela
dc.contributor.authorDeStefano, Anita L
dc.contributor.authorSchneider, Anja
dc.contributor.authorHaapasalo, Annakaisa
dc.contributor.authorKinhult Ståhlbom, Anne
dc.contributor.authorTybjærg-Hansen, Anne
dc.contributor.authorHartmann, Annette M
dc.contributor.authorSpottke, Annika
dc.contributor.authorCorbatón-Anchuelo, Arturo
dc.contributor.authorRongve, Arvid
dc.contributor.authorBorroni, Barbara
dc.contributor.authorArosio, Beatrice
dc.contributor.authorNacmias, Benedetta
dc.contributor.authorNordestgaard, Børge G
dc.contributor.authorKunkle, Brian W
dc.contributor.authorCharbonnier, Camille
dc.contributor.authorAbdelnour, Carla
dc.contributor.authorMasullo, Carlo
dc.contributor.authorMartínez Rodríguez, Carmen
dc.contributor.authorMuñoz-Fernandez, Carmen
dc.contributor.authorDufouil, Carole
dc.contributor.authorGraff, Caroline
dc.contributor.authorFerreira, Catarina B
dc.contributor.authorChillotti, Caterina
dc.contributor.authorReynolds, Chandra A
dc.contributor.authorFenoglio, Chiara
dc.contributor.authorVan Broeckhoven, Christine
dc.contributor.authorClark, Christopher
dc.contributor.authorPisanu, Claudia
dc.contributor.authorSatizabal, Claudia L
dc.contributor.authorHolmes, Clive
dc.contributor.authorBuiza-Rueda, Dolores
dc.contributor.authorAarsland, Dag
dc.contributor.authorRujescu, Dan
dc.contributor.authorAlcolea, Daniel
dc.contributor.authorGalimberti, Daniela
dc.contributor.authorWallon, David
dc.contributor.authorSeripa, Davide
dc.contributor.authorGrünblatt, Edna
dc.contributor.authorDardiotis, Efthimios
dc.contributor.authorDüzel, Emrah
dc.contributor.authorScarpini, Elio
dc.contributor.authorConti, Elisa
dc.contributor.authorRubino, Elisa
dc.contributor.authorGelpi, Ellen
dc.contributor.authorRodriguez-Rodriguez, Eloy
dc.contributor.authorDuron, Emmanuelle
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorFerri, Evelyn
dc.contributor.authorTagliavini, Fabrizio
dc.contributor.authorKüçükali, Fahri
dc.contributor.authorPasquier, Florence
dc.contributor.authorSanchez-Garcia, Florentino
dc.contributor.authorMangialasche, Francesca
dc.contributor.authorJessen, Frank
dc.contributor.authorNicolas, Gaël
dc.contributor.authorSelbæk, Geir
dc.contributor.authorOrtega, Gemma
dc.contributor.authorChêne, Geneviève
dc.contributor.authorHadjigeorgiou, Georgios
dc.contributor.authorRossi, Giacomina
dc.contributor.authorSpalletta, Gianfranco
dc.contributor.authorGiaccone, Giorgio
dc.contributor.authorGrande, Giulia
dc.contributor.authorBinetti, Giuliano
dc.contributor.authorPapenberg, Goran
dc.contributor.authorHampel, Harald
dc.contributor.authorBailly, Henri
dc.contributor.authorZetterberg, Henrik
dc.contributor.authorSoininen, Hilkka
dc.contributor.authorKarlsson, Ida K
dc.contributor.authorAlvarez, Ignacio
dc.contributor.authorAppollonio, Ildebrando
dc.contributor.authorGiegling, Ina
dc.contributor.authorSkoog, Ingmar
dc.contributor.authorSaltvedt, Ingvild
dc.contributor.authorRainero, Innocenzo
dc.contributor.authorRosas Allende, Irene
dc.contributor.authorHort, Jakub
dc.contributor.authorDiehl-Schmid, Janine
dc.contributor.authorVan Dongen, Jasper
dc.contributor.authorVidal, Jean-Sebastien
dc.contributor.authorLehtisalo, Jenni
dc.contributor.authorWiltfang, Jens
dc.contributor.authorThomassen, Jesper Qvist
dc.contributor.authorKornhuber, Johannes
dc.contributor.authorHaines, Jonathan L
dc.contributor.authorVogelgsang, Jonathan
dc.contributor.authorPineda, Juan A
dc.contributor.authorFortea, Juan
dc.contributor.authorPopp, Julius
dc.contributor.authorDeckert, Jürgen
dc.contributor.authorBuerger, Katharina
dc.contributor.authorMorgan, Kevin
dc.contributor.authorFließbach, Klaus
dc.contributor.authorSleegers, Kristel
dc.contributor.authorMolina-Porcel, Laura
dc.contributor.authorKilander, Lena
dc.contributor.authorWeinhold, Leonie
dc.contributor.authorFarrer, Lindsay A
dc.contributor.authorWang, Li-San
dc.contributor.authorKleineidam, Luca
dc.contributor.authorFarotti, Lucia
dc.contributor.authorParnetti, Lucilla
dc.contributor.authorTremolizzo, Lucio
dc.contributor.authorHausner, Lucrezia
dc.contributor.authorBenussi, Luisa
dc.contributor.authorFroelich, Lutz
dc.contributor.authorIkram, M Arfan
dc.contributor.authorDeniz-Naranjo, M Candida
dc.contributor.authorTsolaki, Magda
dc.contributor.authorRosende-Roca, Maitée
dc.contributor.authorLöwenmark, Malin
dc.contributor.authorHulsman, Marc
dc.contributor.authorSpallazzi, Marco
dc.contributor.authorPericak-Vance, Margaret A
dc.contributor.authorEsiri, Margaret
dc.contributor.authorBernal Sánchez-Arjona, María
dc.contributor.authorDalmasso, Maria Carolina
dc.contributor.authorMartínez-Larrad, María Teresa
dc.contributor.authorArcaro, Marina
dc.contributor.authorNöthen, Markus M
dc.contributor.authorFernández-Fuertes, Marta
dc.contributor.authorDichgans, Martin
dc.contributor.authorIngelsson, Martin
dc.contributor.authorHerrmann, Martin J
dc.contributor.authorScherer, Martin
dc.contributor.authorVyhnalek, Martin
dc.contributor.authorKosmidis, Mary H
dc.contributor.authorYannakoulia, Mary
dc.contributor.authorSchmid, Matthias
dc.contributor.authorEwers, Michael
dc.contributor.authorHeneka, Michael T
dc.contributor.authorWagner, Michael
dc.contributor.authorScamosci, Michela
dc.contributor.authorKivipelto, Miia
dc.contributor.authorHiltunen, Mikko
dc.contributor.authorZulaica, Miren
dc.contributor.authorAlegret, Montserrat
dc.contributor.authorFornage, Myriam
dc.contributor.authorRoberto, Natalia
dc.contributor.authorvan Schoor, Natasja M
dc.contributor.authorSeidu, Nazib M
dc.contributor.authorBanaj, Nerisa
dc.contributor.authorArmstrong, Nicola J
dc.contributor.authorScarmeas, Nikolaos
dc.contributor.authorScherbaum, Norbert
dc.contributor.authorGoldhardt, Oliver
dc.contributor.authorHanon, Oliver
dc.contributor.authorPeters, Oliver
dc.contributor.authorSkrobot, Olivia Anna
dc.contributor.authorQuenez, Olivier
dc.contributor.authorLerch, Ondrej
dc.contributor.authorBossù, Paola
dc.contributor.authorCaffarra, Paolo
dc.contributor.authorDionigi Rossi, Paolo
dc.contributor.authorSakka, Paraskevi
dc.contributor.authorHoffmann, Per
dc.contributor.authorHolmans, Peter A
dc.contributor.authorFischer, Peter
dc.contributor.authorRiederer, Peter
dc.contributor.authorYang, Qiong
dc.contributor.authorMarshall, Rachel
dc.contributor.authorKalaria, Rajesh N
dc.contributor.authorMayeux, Richard
dc.contributor.authorVandenberghe, Rik
dc.contributor.authorCecchetti, Roberta
dc.contributor.authorGhidoni, Roberta
dc.contributor.authorFrikke-Schmidt, Ruth
dc.contributor.authorSorbi, Sandro
dc.contributor.authorHägg, Sara
dc.contributor.authorEngelborghs, Sebastiaan
dc.contributor.authorHelisalmi, Seppo
dc.contributor.authorBotne Sando, Sigrid
dc.contributor.authorKern, Silke
dc.contributor.authorArchetti, Silvana
dc.contributor.authorBoschi, Silvia
dc.contributor.authorFostinelli, Silvia
dc.contributor.authorGil, Silvia
dc.contributor.authorMendoza, Silvia
dc.contributor.authorMead, Simon
dc.contributor.authorCiccone, Simona
dc.contributor.authorDjurovic, Srdjan
dc.contributor.authorHeilmann-Heimbach, Stefanie
dc.contributor.authorRiedel-Heller, Steffi
dc.contributor.authorKuulasmaa, Teemu
dc.contributor.authorDel Ser, Teodoro
dc.contributor.authorLebouvier, Thibaud
dc.contributor.authorPolak, Thomas
dc.contributor.authorNgandu, Tiia
dc.contributor.authorGrimmer, Timo
dc.contributor.authorBessi, Valentina
dc.contributor.authorEscott-Price, Valentina
dc.contributor.authorGiedraitis, Vilmantas
dc.contributor.authorDeramecourt, Vincent
dc.contributor.authorMaier, Wolfgang
dc.contributor.authorJian, Xueqiu
dc.contributor.authorPijnenburg, Yolande A L
dc.contributor.authorKehoe, Patrick Gavin
dc.contributor.authorGarcia-Ribas, Guillermo
dc.contributor.authorSánchez-Juan, Pascual
dc.contributor.authorPastor, Pau
dc.contributor.authorPérez-Tur, Jordi
dc.contributor.authorPiñol-Ripoll, Gerard
dc.contributor.authorLopez de Munain, Adolfo
dc.contributor.authorGarcía-Alberca, Jose María
dc.contributor.authorBullido, María J
dc.contributor.authorÁlvarez, Victoria
dc.contributor.authorLleó, Alberto
dc.contributor.authorReal, Luis M
dc.contributor.authorMir, Pablo
dc.contributor.authorMedina, Miguel
dc.contributor.authorScheltens, Philip
dc.contributor.authorHolstege, Henne
dc.contributor.authorMarquié, Marta
dc.contributor.authorSáez, María Eugenia
dc.contributor.authorCarracedo, Ángel
dc.contributor.authorAmouyel, Philippe
dc.contributor.authorSchellenberg, Gerard D
dc.contributor.authorWilliams, Julie
dc.contributor.authorSeshadri, Sudha
dc.contributor.authorvan Duijn, Cornelia M
dc.contributor.authorMather, Karen A
dc.contributor.authorSánchez-Valle, Raquel
dc.contributor.authorSerrano-Ríos, Manuel
dc.contributor.authorOrellana, Adelina
dc.contributor.authorTárraga, Lluís
dc.contributor.authorBlennow, Kaj
dc.contributor.authorHuisman, Martijn
dc.contributor.authorAndreassen, Ole A
dc.contributor.authorPosthuma, Danielle
dc.contributor.authorClarimón, Jordi
dc.contributor.authorBoada, Mercè
dc.contributor.authorvan der Flier, Wiesje M
dc.contributor.authorRamirez, Alfredo
dc.contributor.authorLambert, Jean-Charles
dc.contributor.authorvan der Lee, Sven J
dc.contributor.authorRuiz, Agustín
dc.date.accessioned2021-12-13T18:42:31Z
dc.date.available2021-12-13T18:42:31Z
dc.date.issued2021
dc.identifier.citationNat Commun . 2021;12(1):3417.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13491
dc.description.abstractGenetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.es_ES
dc.description.sponsorshipWe would like to thank patients and controls who participated in this project. The present work has been performed as part of the doctoral program of I. de Rojas at the Universitat de Barcelona (Barcelona, Spain) supported by national grant from the Instituto de Salud Carlos III FI20/00215. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria “La Caixa”, Fundació ACE, and CIBERNED. A.R. and M.B. receive support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). M.B. and A.R. are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240 and PI19/01301. Acción Estratégica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)—Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER—“Una manera de hacer Europa”). Some control samples and data from patients included in this study were provided in part by the National DNA Bank Carlos III (www.bancoadn.org, University of Salamanca, Spain) and Hospital Universitario Virgen de Valme (Sevilla, Spain); they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. Amsterdam dementia Cohort (ADC): Research of the Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Genotyping of the Dutch case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). 100-Plus study: We are grateful for the collaborative efforts of all participating centenarians and their family members and/or relations. This work was supported by Stichting Alzheimer Nederland (WE09.2014-03), Stichting Diorapthe, horstingstuit foundation, Memorabel (ZonMW project number 733050814, 733050512) and Stichting VUmc Fonds. Genotyping of the 100-Plus Study was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). Longitudinal Aging Study Amsterdam (LASA) is largely supported by a grant from the Netherlands Ministry of Health, Welfare and Sports, Directorate of Long-Term Care. The authors are grateful to all LASA participants, the fieldwork team and all researchers for their ongoing commitment to the study. This work was supported by a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Program—Neurodegenerative Disease Research (JPND) and also funded by Inserm, Institut Pasteur de Lille, the Lille Métropole Communauté Urbaine, the French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Genotyping of the German case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND (German Federal Ministry of Education and Research, BMBF: 01ED1619A). Full acknowledgments for the studies that contributed data can be found in the Supplementary Note. We thank the numerous participants, researchers, and staff from many studies who collected and contributed to the data. We thank the International Genomics of Alzheimer’s Project (IGAP) for providing summary results data for these analyses. The investigators within IGAP contributed to the design and implementation of IGAP and/or provided data but did not participate in analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients, and their families. The i–Select chips was funded by the French National Foundation on AD and related disorders. EADI was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Université de Lille 2 and the Lille University Hospital. GERAD was supported by the Medical Research Council (Grant n° 503480), Alzheimer’s Research UK (Grant n° 503176), the Wellcome Trust (Grant n° 082604/2/07/Z) and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant n° 01GI0102, 01GI0711, 01GI0420. CHARGE was partly supported by the NIA/NHLBI grants AG049505, AG058589, HL105756 and AGES contract N01–AG–12100, the Icelandic Heart Association, and the Erasmus Medical Center and Erasmus University. ADGC was supported by the NIH/NIA grants: U01 AG032984, U24 AG021886, U01 AG016976, and the Alzheimer’s Association grant ADGC–10–196728. This research has been conducted using the UK Biobank public resource obtained through the University of Edinburg Data Share (https://datashare.is.ed.ac.uk/handle/10283/3364).es_ES
dc.language.isoenges_ES
dc.publisherNature Research [Commercial Pes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshMultifactorial Inheritance es_ES
dc.subject.meshAge of Onset es_ES
dc.subject.meshAged es_ES
dc.subject.meshAged, 80 and over es_ES
dc.subject.meshAlzheimer Disease es_ES
dc.subject.meshAmyloid beta-Protein Precursor es_ES
dc.subject.meshApolipoproteins E es_ES
dc.subject.meshCase-Control Studies es_ES
dc.subject.meshCohort Studies es_ES
dc.subject.meshDatasets as Topic es_ES
dc.subject.meshFemale es_ES
dc.subject.meshFollow-Up Studies es_ES
dc.subject.meshGenetic Predisposition to Disease es_ES
dc.subject.meshGenome-Wide Association Study es_ES
dc.subject.meshHeterozygote es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMale es_ES
dc.subject.meshMiddle Aged es_ES
dc.subject.meshPolymorphism, Single Nucleotidees_ES
dc.subject.meshRisk Assessment es_ES
dc.subject.meshRisk Factors es_ES
dc.titleCommon variants in Alzheimer's disease and risk stratification by polygenic risk scores.es_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID34099642es_ES
dc.format.volume12es_ES
dc.format.number1es_ES
dc.format.page3417es_ES
dc.identifier.doi10.1038/s41467-021-22491-8es_ES
dc.contributor.funderInstituto de Salud Carlos IIIes_ES
dc.contributor.funderEuropean Commissiones_ES
dc.contributor.funderFundació ACEes_ES
dc.contributor.funderFundación La Caixaes_ES
dc.contributor.funderGrifolses_ES
dc.contributor.funderCentro de Investigación Biomedica en Red - CIBERes_ES
dc.contributor.funderStichting Alzheimer Nederlandes_ES
dc.contributor.funderStichting Diorapthees_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-021-22491-8es_ES
dc.identifier.journalNature Communicationses_ES
dc.repisalud.centroISCIII::Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)es_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/115975/EUes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/115985/EUes_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.relation.projectFISinfo:fis/Instituto de Salud Carlos III/null/null/Subprograma de proyectos de investigacion en salud (AES 2013) (2013)/PI13/02434es_ES
dc.relation.projectFISinfo:fis/Instituto de Salud Carlos III/Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia/Subprograma Estatal de Generación de Conocimiento/Proyectos de investigacion en salud (AES 2016). Modalidad proyectos en salud. (2016)/PI16/01861es_ES
dc.relation.projectFISinfo:fis/Instituto de Salud Carlos III/Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia/Subprograma Estatal de Generación de Conocimiento/PI17 - Proyectos de investigacion en salud (AES 2017). Modalidad proyectos en salud. (2017)/PI17/01474es_ES
dc.relation.projectFISinfo:fis/Instituto de Salud Carlos III/Programa Estatal de Generación de Conocimiento y Fortalecimiento del Sistema Español de I+D+I/Subprograma Estatal de Generación de Conocimiento/PI19 - Proyectos de investigacion en salud (AES 2019). Modalidad proyectos en salud. (2019)/PI19/01301es_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/FI20/00215es_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/PI19/01240es_ES


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