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

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dc.contributor.authorBellenguez, Céline
dc.contributor.authorKüçükali, Fahri
dc.contributor.authorJansen, Iris E.
dc.contributor.authorKleineidam, Luca
dc.contributor.authorMoreno-Grau, Sonia
dc.contributor.authorAmin, Najaf
dc.contributor.authorNaj, Adam C.
dc.contributor.authorCampos-Martin, Rafael
dc.contributor.authorGrenier-Boley, Benjamin
dc.contributor.authorAndrade, Victor
dc.contributor.authorHolmans, Peter A.
dc.contributor.authorBoland, Anne
dc.contributor.authorDamotte, Vincent
dc.contributor.authorvan der Lee, Sven J.
dc.contributor.authorCosta, Marcos R.
dc.contributor.authorKuulasmaa, Teemu
dc.contributor.authorYang, Qiong
dc.contributor.authorde Rojas, Itziar
dc.contributor.authorBis, Joshua C.
dc.contributor.authorYaqub, Amber
dc.contributor.authorProkic, Ivana
dc.contributor.authorChapuis, Julien
dc.contributor.authorAhmad, Shahzad
dc.contributor.authorGiedraitis, Vilmantas
dc.contributor.authorAarsland, Dag
dc.contributor.authorGarcia-Gonzalez, Pablo
dc.contributor.authorAbdelnour, Carla
dc.contributor.authorAlarcón-Martín, Emilio
dc.contributor.authorAlcolea, Daniel
dc.contributor.authorAlegret, Montserrat
dc.contributor.authorAlvarez, Ignacio
dc.contributor.authorÁlvarez, Victoria
dc.contributor.authorArmstrong, Nicola J.
dc.contributor.authorTsolaki, Anthoula
dc.contributor.authorAntúnez, Carmen
dc.contributor.authorAppollonio, Ildebrando
dc.contributor.authorArcaro, Marina
dc.contributor.authorArchetti, Silvana
dc.contributor.authorArias Pastor, Alfonso
dc.contributor.authorArosio, Beatrice
dc.contributor.authorAthanasiu, Lavinia
dc.contributor.authorBailly, Henri
dc.contributor.authorBanaj, Nerisa
dc.contributor.authorBaquero, Miquel
dc.contributor.authorBarral, Sandra
dc.contributor.authorBeiser, Alexa
dc.contributor.authorBelén Pastor, Ana
dc.contributor.authorBelow, Jennifer E.
dc.contributor.authorBenchek, Penelope
dc.contributor.authorBenussi, Luisa
dc.contributor.authorBerr, Claudine
dc.contributor.authorBesse, Céline
dc.contributor.authorBessi, Valentina
dc.contributor.authorBinetti, Giuliano
dc.contributor.authorBizarro, Alessandra
dc.contributor.authorBlesa, Rafael
dc.contributor.authorBoada, Mercè
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorBorroni, Barbara
dc.contributor.authorBoschi, Silvia
dc.contributor.authorBossù, Paola
dc.contributor.authorBråthen, Geir
dc.contributor.authorBressler, Jan
dc.contributor.authorBresner, Catherine
dc.contributor.authorBrodaty, Henry
dc.contributor.authorBrookes, Keeley J.
dc.contributor.authorBrusco, Luis Ignacio
dc.contributor.authorBuiza-Rueda, Dolores
dc.contributor.authorBûrger, Katharina
dc.contributor.authorBurholt, Vanessa
dc.contributor.authorBush, William S.
dc.contributor.authorCalero, Miguel
dc.contributor.authorCantwell, Laura B.
dc.contributor.authorChene, Geneviève
dc.contributor.authorChung, Jaeyoon
dc.contributor.authorCuccaro, Michael L.
dc.contributor.authorCarracedo, Ángel
dc.contributor.authorCecchetti, Roberta
dc.contributor.authorCervera-Carles, Laura
dc.contributor.authorCharbonnier, Camille
dc.contributor.authorChen, Hung-Hsin
dc.contributor.authorChillotti, Caterina
dc.contributor.authorCiccone, Simona
dc.contributor.authorClaassen, Jurgen A. H. R.
dc.contributor.authorClark, Christopher
dc.contributor.authorConti, Elisa
dc.contributor.authorCorma-Gómez, Anaïs
dc.contributor.authorCostantini, Emanuele
dc.contributor.authorCustodero, Carlo
dc.contributor.authorDaian, Delphine
dc.contributor.authorDalmasso, Maria Carolina
dc.contributor.authorDaniele, Antonio
dc.contributor.authorDardiotis, Efthimios
dc.contributor.authorDartigues, Jean-François
dc.contributor.authorde Deyn, Peter Paul
dc.contributor.authorde Paiva Lopes, Katia
dc.contributor.authorde Witte, Lot D.
dc.contributor.authorDebette, Stéphanie
dc.contributor.authorDeckert, Jürgen
dc.contributor.authorDel Ser, Teodoro
dc.contributor.authorDenning, Nicola
dc.contributor.authorDeStefano, Anita
dc.contributor.authorDichgans, Martin
dc.contributor.authorDiehl-Schmid, Janine
dc.contributor.authorDiez-Fairen, Mónica
dc.contributor.authorDionigi Rossi, Paolo
dc.contributor.authorDjurovic, Srdjan
dc.contributor.authorDuron, Emmanuelle
dc.contributor.authorDüzel, Emrah
dc.contributor.authorDufouil, Carole
dc.contributor.authorEiriksdottir, Gudny
dc.contributor.authorEngelborghs, Sebastiaan
dc.contributor.authorEscott-Price, Valentina
dc.contributor.authorEspinosa, Ana
dc.contributor.authorEwers, Michael
dc.contributor.authorFaber, Kelley M.
dc.contributor.authorFabrizio, Tagliavini
dc.contributor.authorFallgaard Nielsen, Sune
dc.contributor.authorFardo, David W.
dc.contributor.authorFarotti, Lucia
dc.contributor.authorFenoglio, Chiara
dc.contributor.authorFernández-Fuertes, Marta
dc.contributor.authorFerrari, Raffaele
dc.contributor.authorFerreira, Catarina B.
dc.contributor.authorFerri, Evelyn
dc.contributor.authorFin, Bertrand
dc.contributor.authorFischer, Peter
dc.contributor.authorFladby, Tormod
dc.contributor.authorFließbach, Klaus
dc.contributor.authorFongang, Bernard
dc.contributor.authorFornage, Myriam
dc.contributor.authorFortea, Juan
dc.contributor.authorForoud, Tatiana M.
dc.contributor.authorFostinelli, Silvia
dc.contributor.authorFox, Nick C.
dc.contributor.authorFranco-Macías, Emlio
dc.contributor.authorBullido, María J.
dc.contributor.authorFrank-García, Ana
dc.contributor.authorFroelich, Lutz
dc.contributor.authorFulton-Howard, Brian
dc.contributor.authorGalimberti, Daniela
dc.contributor.authorGarcía-Alberca, Jose Maria
dc.contributor.authorGarcía-González, Pablo
dc.contributor.authorGarcia-Madrona, Sebastian
dc.contributor.authorGarcia-Ribas, Guillermo
dc.contributor.authorGhidoni, Roberta
dc.contributor.authorGiegling, Ina
dc.contributor.authorGiorgio, Giaccone
dc.contributor.authorGoate, Alison M.
dc.contributor.authorGoldhardt, Oliver
dc.contributor.authorGomez-Fonseca, Duber
dc.contributor.authorGonzález-Pérez, Antonio
dc.contributor.authorGraff, Caroline
dc.contributor.authorGrande, Giulia
dc.contributor.authorGreen, Emma
dc.contributor.authorGrimmer, Timo
dc.contributor.authorGrünblatt, Edna
dc.contributor.authorGrunin, Michelle
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorGuetta-Baranes, Tamar
dc.contributor.authorHaapasalo, Annakaisa
dc.contributor.authorHadjigeorgiou, Georgios
dc.contributor.authorHaines, Jonathan L.
dc.contributor.authorHamilton-Nelson, Kara L.
dc.contributor.authorHampel, Harald
dc.contributor.authorHanon, Olivier
dc.contributor.authorHardy, John
dc.contributor.authorHartmann, Annette M.
dc.contributor.authorHausner, Lucrezia
dc.contributor.authorHarwood, Janet
dc.contributor.authorHeilmann-Heimbach, Stefanie
dc.contributor.authorHelisalmi, Seppo
dc.contributor.authorHeneka, Michael T.
dc.contributor.authorHernández, Isabel
dc.contributor.authorHerrmann, Martin J.
dc.contributor.authorHoffmann, Per
dc.contributor.authorHolmes, Clive
dc.contributor.authorHolstege, Henne
dc.contributor.authorHuerto Vilas, Raquel
dc.contributor.authorHulsman, Marc
dc.contributor.authorHumphrey, Jack
dc.contributor.authorJan Biessels, Geert
dc.contributor.authorJian, Xueqiu
dc.contributor.authorJohansson, Charlotte
dc.contributor.authorJun, Gyungah R.
dc.contributor.authorKastumata, Yuriko
dc.contributor.authorKauwe, John
dc.contributor.authorKehoe, Patrick G.
dc.contributor.authorKilander, Lena
dc.contributor.authorKinhult Ståhlbom, Anne
dc.contributor.authorKivipelto, Miia
dc.contributor.authorKoivisto, Anne
dc.contributor.authorKornhuber, Johannes
dc.contributor.authorKosmidis, Mary H.
dc.contributor.authorKukull, Walter A.
dc.contributor.authorKuksa, Pavel P.
dc.contributor.authorKunkle, Brian W.
dc.contributor.authorKuzma, Amanda B.
dc.contributor.authorLage, Carmen
dc.contributor.authorLaukka, Erika J.
dc.contributor.authorLauner, Lenore
dc.contributor.authorLauria, Alessandra
dc.contributor.authorLee, Chien-Yueh
dc.contributor.authorLehtisalo, Jenni
dc.contributor.authorLerch, Ondrej
dc.contributor.authorLleó, Alberto
dc.contributor.authorLongstreth, William, Jr.
dc.contributor.authorLopez, Oscar
dc.contributor.authorLopez de Munain, Adolfo
dc.contributor.authorLove, Seth
dc.contributor.authorLöwemark, Malin
dc.contributor.authorLuckcuck, Lauren
dc.contributor.authorLunetta, Kathryn L.
dc.contributor.authorMa, Yiyi
dc.contributor.authorMacías, Juan
dc.contributor.authorMacLeod, Catherine A.
dc.contributor.authorMaier, Wolfgang
dc.contributor.authorMangialasche, Francesca
dc.contributor.authorSpallazzi, Marco
dc.contributor.authorMarquié, Marta
dc.contributor.authorMarshall, Rachel
dc.contributor.authorMartin, Eden R.
dc.contributor.authorMartín Montes, Angel
dc.contributor.authorMartínez Rodríguez, Carmen
dc.contributor.authorMasullo, Carlo
dc.contributor.authorMayeux, Richard
dc.contributor.authorMead, Simon
dc.contributor.authorMecocci, Patrizia
dc.contributor.authorMedina, Miguel
dc.contributor.authorMeggy, Alun
dc.contributor.authorMehrabian, Shima
dc.contributor.authorMendoza, Silvia
dc.contributor.authorMenéndez-González, Manuel
dc.contributor.authorMir, Pablo
dc.contributor.authorMoebus, Susanne
dc.contributor.authorMol, Merel
dc.contributor.authorMolina-Porcel, Laura
dc.contributor.authorMontrreal, Laura
dc.contributor.authorMorelli, Laura
dc.contributor.authorMoreno, Fermin
dc.contributor.authorMorgan, Kevin
dc.contributor.authorMosley, Thomas
dc.contributor.authorNöthen, Markus M.
dc.contributor.authorMuchnik, Carolina
dc.contributor.authorMukherjee, Shubhabrata
dc.contributor.authorNacmias, Benedetta
dc.contributor.authorNgandu, Tiia
dc.contributor.authorNicolas, Gael
dc.contributor.authorNordestgaard, Børge G.
dc.contributor.authorOlaso, Robert
dc.contributor.authorOrellana, Adelina
dc.contributor.authorOrsini, Michela
dc.contributor.authorOrtega, Gemma
dc.contributor.authorPadovani, Alessandro
dc.contributor.authorPaolo, Caffarra
dc.contributor.authorPapenberg, Goran
dc.contributor.authorParnetti, Lucilla
dc.contributor.authorPasquier, Florence
dc.contributor.authorPastor, Pau
dc.contributor.authorPeloso, Gina
dc.contributor.authorPérez-Cordón, Alba
dc.contributor.authorPérez-Tur, Jordi
dc.contributor.authorPericard, Pierre
dc.contributor.authorPeters, Oliver
dc.contributor.authorPijnenburg, Yolande A. L.
dc.contributor.authorPineda, Juan A.
dc.contributor.authorPiñol-Ripoll, Gerard
dc.contributor.authorPisanu, Claudia
dc.contributor.authorPolak, Thomas
dc.contributor.authorPopp, Julius
dc.contributor.authorPosthuma, Danielle
dc.contributor.authorPriller, Josef
dc.contributor.authorPuerta, Raquel
dc.contributor.authorQuenez, Olivier
dc.contributor.authorQuintela, Inés
dc.contributor.authorQvist Thomassen, Jesper
dc.contributor.authorRábano, Alberto
dc.contributor.authorRainero, Innocenzo
dc.contributor.authorRajabli, Farid
dc.contributor.authorRamakers, Inez
dc.contributor.authorReal, Luis M.
dc.contributor.authorReinders, Marcel J. T.
dc.contributor.authorReitz, Christiane
dc.contributor.authorReyes-Dumeyer, Dolly
dc.contributor.authorRidge, Perry
dc.contributor.authorRiedel-Heller, Steffi
dc.contributor.authorRiederer, Peter
dc.contributor.authorRoberto, Natalia
dc.contributor.authorRodriguez-Rodriguez, Eloy
dc.contributor.authorRongve, Arvid
dc.contributor.authorRosas Allende, Irene
dc.contributor.authorRosende-Roca, Maitée
dc.contributor.authorRoyo, Jose Luis
dc.contributor.authorRubino, Elisa
dc.contributor.authorRujescu, Dan
dc.contributor.authorSáez, María Eugenia
dc.contributor.authorSakka, Paraskevi
dc.contributor.authorSaltvedt, Ingvild
dc.contributor.authorSanabria, Ángela
dc.contributor.authorSánchez-Arjona, María Bernal
dc.contributor.authorSanchez-Garcia, Florentino
dc.contributor.authorSánchez Juan, Pascual
dc.contributor.authorSánchez-Valle, Raquel
dc.contributor.authorSando, Sigrid B.
dc.contributor.authorSarnowski, Chloé
dc.contributor.authorSatizabal, Claudia L.
dc.contributor.authorScamosci, Michela
dc.contributor.authorScarmeas, Nikolaos
dc.contributor.authorScarpini, Elio
dc.contributor.authorScheltens, Philip
dc.contributor.authorScherbaum, Norbert
dc.contributor.authorScherer, Martin
dc.contributor.authorSchmid, Matthias
dc.contributor.authorSchneider, Anja
dc.contributor.authorSchott, Jonathan M.
dc.contributor.authorSelbæk, Geir
dc.contributor.authorSeripa, Davide
dc.contributor.authorSerrano, Manuel
dc.contributor.authorSha, Jin
dc.contributor.authorShadrin, Alexey A.
dc.contributor.authorSkrobot, Olivia
dc.contributor.authorSlifer, Susan
dc.contributor.authorSnijders, Gijsje J. L.
dc.contributor.authorSoininen, Hilkka
dc.contributor.authorSolfrizzi, Vincenzo
dc.contributor.authorSolomon, Alina
dc.contributor.authorSong, Yeunjoo
dc.contributor.authorSorbi, Sandro
dc.contributor.authorSotolongo-Grau, Oscar
dc.contributor.authorSpalletta, Gianfranco
dc.contributor.authorSpottke, Annika
dc.contributor.authorSquassina, Alessio
dc.contributor.authorStordal, Eystein
dc.contributor.authorTartan, Juan Pablo
dc.contributor.authorTárraga, Lluís
dc.contributor.authorTesí, Niccolo
dc.contributor.authorThalamuthu, Anbupalam
dc.contributor.authorThomas, Tegos
dc.contributor.authorTosto, Giuseppe
dc.contributor.authorTraykov, Latchezar
dc.contributor.authorTremolizzo, Lucio
dc.contributor.authorTybjærg-Hansen, Anne
dc.contributor.authorUitterlinden, Andre
dc.contributor.authorUllgren, Abbe
dc.contributor.authorUlstein, Ingun
dc.contributor.authorValero, Sergi
dc.contributor.authorValladares, Otto
dc.contributor.authorVan Broeckhoven, Christine
dc.contributor.authorVance, Jeffery
dc.contributor.authorVardarajan, Badri N.
dc.contributor.authorvan der Lugt, Aad
dc.contributor.authorVan Dongen, Jasper
dc.contributor.authorvan Rooij, Jeroen
dc.contributor.authorvan Swieten, John
dc.contributor.authorVandenberghe, Rik
dc.contributor.authorVerhey, Frans
dc.contributor.authorVidal, Jean-Sébastien
dc.contributor.authorVogelgsang, Jonathan
dc.contributor.authorVyhnalek, Martin
dc.contributor.authorWagner, Michael
dc.contributor.authorWallon, David
dc.contributor.authorWang, Li-San
dc.contributor.authorWang, Ruiqi
dc.contributor.authorWeinhold, Leonie
dc.contributor.authorWiltfang, Jens
dc.contributor.authorWindle, Gill
dc.contributor.authorWoods, Bob
dc.contributor.authorYannakoulia, Mary
dc.contributor.authorZare, Habil
dc.contributor.authorZhao, Yi
dc.contributor.authorZhang, Xiaoling
dc.contributor.authorZhu, Congcong
dc.contributor.authorZulaica, Miren
dc.contributor.authorEADB
dc.contributor.authorGR@ACE
dc.contributor.authorDEGESCO
dc.contributor.authorEADI
dc.contributor.authorGERAD
dc.contributor.authorDemgene
dc.contributor.authorFinnGen
dc.contributor.authorADGC
dc.contributor.authorCHARGE
dc.contributor.authorFarrer, Lindsay A.
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorGhanbari, Mohsen
dc.contributor.authorRaj, Towfique
dc.contributor.authorSachdev, Perminder
dc.contributor.authorMather, Karen
dc.contributor.authorJessen, Frank
dc.contributor.authorIkram, M. Arfan
dc.contributor.authorde Mendonça, Alexandre
dc.contributor.authorHort, Jakub
dc.contributor.authorTsolaki, Magda
dc.contributor.authorPericak-Vance, Margaret A.
dc.contributor.authorAmouyel, Philippe
dc.contributor.authorWilliams, Julie
dc.contributor.authorFrikke-Schmidt, Ruth
dc.contributor.authorClarimon, Jordi
dc.contributor.authorDeleuze, Jean-François
dc.contributor.authorRossi, Giacomina
dc.contributor.authorSeshadri, Sudha
dc.contributor.authorAndreassen, Ole A.
dc.contributor.authorIngelsson, Martin
dc.contributor.authorHiltunen, Mikko
dc.contributor.authorSleegers, Kristel
dc.contributor.authorSchellenberg, Gerard D.
dc.contributor.authorvan Duijn, Cornelia M.
dc.contributor.authorSims, Rebecca
dc.contributor.authorvan der Flier, Wiesje M.
dc.contributor.authorRuiz, Agustín
dc.contributor.authorRamirez, Alfredo
dc.contributor.authorLambert, Jean-Charles
dc.contributor.departmentMedical and Molecular Genetics, School of Medicine
dc.date.accessioned2024-05-06T18:50:02Z
dc.date.available2024-05-06T18:50:02Z
dc.date.issued2022
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 ε4 allele.
dc.eprint.versionFinal published version
dc.identifier.citationBellenguez C, Küçükali F, Jansen IE, et al. New insights into the genetic etiology of Alzheimer's disease and related dementias. Nat Genet. 2022;54(4):412-436. doi:10.1038/s41588-022-01024-z
dc.identifier.urihttps://hdl.handle.net/1805/40501
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isversionof10.1038/s41588-022-01024-z
dc.relation.journalNature Genetics
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePMC
dc.subjectAlzheimer's disease
dc.subjectGenome-wide association studies
dc.subjectCognitive dysfunction
dc.titleNew insights into the genetic etiology of Alzheimer's disease and related dementias
dc.typeArticle
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