Bellenguez, CélineKüçükali, FahriJansen, Iris E.Kleineidam, LucaMoreno-Grau, SoniaAmin, NajafNaj, Adam C.Campos-Martin, RafaelGrenier-Boley, BenjaminAndrade, VictorHolmans, Peter A.Boland, AnneDamotte, Vincentvan der Lee, Sven J.Costa, Marcos R.Kuulasmaa, TeemuYang, Qiongde Rojas, ItziarBis, Joshua C.Yaqub, AmberProkic, IvanaChapuis, JulienAhmad, ShahzadGiedraitis, VilmantasAarsland, DagGarcia-Gonzalez, PabloAbdelnour, CarlaAlarcón-Martín, EmilioAlcolea, DanielAlegret, MontserratAlvarez, IgnacioÁlvarez, VictoriaArmstrong, Nicola J.Tsolaki, AnthoulaAntúnez, CarmenAppollonio, IldebrandoArcaro, MarinaArchetti, SilvanaArias Pastor, AlfonsoArosio, BeatriceAthanasiu, LaviniaBailly, HenriBanaj, NerisaBaquero, MiquelBarral, SandraBeiser, AlexaBelén Pastor, AnaBelow, Jennifer E.Benchek, PenelopeBenussi, LuisaBerr, ClaudineBesse, CélineBessi, ValentinaBinetti, GiulianoBizarro, AlessandraBlesa, RafaelBoada, MercèBoerwinkle, EricBorroni, BarbaraBoschi, SilviaBossù, PaolaBråthen, GeirBressler, JanBresner, CatherineBrodaty, HenryBrookes, Keeley J.Brusco, Luis IgnacioBuiza-Rueda, DoloresBûrger, KatharinaBurholt, VanessaBush, William S.Calero, MiguelCantwell, Laura B.Chene, GenevièveChung, JaeyoonCuccaro, Michael L.Carracedo, ÁngelCecchetti, RobertaCervera-Carles, LauraCharbonnier, CamilleChen, Hung-HsinChillotti, CaterinaCiccone, SimonaClaassen, Jurgen A. 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R.Clark, ChristopherConti, ElisaCorma-Gómez, AnaïsCostantini, EmanueleCustodero, CarloDaian, DelphineDalmasso, Maria CarolinaDaniele, AntonioDardiotis, EfthimiosDartigues, Jean-Françoisde Deyn, Peter Paulde Paiva Lopes, Katiade Witte, Lot D.Debette, StéphanieDeckert, JürgenDel Ser, TeodoroDenning, NicolaDeStefano, AnitaDichgans, MartinDiehl-Schmid, JanineDiez-Fairen, MónicaDionigi Rossi, PaoloDjurovic, SrdjanDuron, EmmanuelleDüzel, EmrahDufouil, CaroleEiriksdottir, GudnyEngelborghs, SebastiaanEscott-Price, ValentinaEspinosa, AnaEwers, MichaelFaber, Kelley M.Fabrizio, TagliaviniFallgaard Nielsen, SuneFardo, David W.Farotti, LuciaFenoglio, ChiaraFernández-Fuertes, MartaFerrari, RaffaeleFerreira, Catarina B.Ferri, EvelynFin, BertrandFischer, PeterFladby, TormodFließbach, KlausFongang, BernardFornage, MyriamFortea, JuanForoud, Tatiana M.Fostinelli, SilviaFox, Nick C.Franco-Macías, EmlioBullido, María J.Frank-García, AnaFroelich, LutzFulton-Howard, BrianGalimberti, DanielaGarcía-Alberca, Jose MariaGarcía-González, PabloGarcia-Madrona, SebastianGarcia-Ribas, GuillermoGhidoni, RobertaGiegling, InaGiorgio, GiacconeGoate, Alison M.Goldhardt, OliverGomez-Fonseca, DuberGonzález-Pérez, AntonioGraff, CarolineGrande, GiuliaGreen, EmmaGrimmer, TimoGrünblatt, EdnaGrunin, MichelleGudnason, VilmundurGuetta-Baranes, TamarHaapasalo, AnnakaisaHadjigeorgiou, GeorgiosHaines, Jonathan L.Hamilton-Nelson, Kara L.Hampel, HaraldHanon, OlivierHardy, JohnHartmann, Annette M.Hausner, LucreziaHarwood, JanetHeilmann-Heimbach, StefanieHelisalmi, SeppoHeneka, Michael T.Hernández, IsabelHerrmann, Martin J.Hoffmann, PerHolmes, CliveHolstege, HenneHuerto Vilas, RaquelHulsman, MarcHumphrey, JackJan Biessels, GeertJian, XueqiuJohansson, CharlotteJun, Gyungah R.Kastumata, YurikoKauwe, JohnKehoe, Patrick G.Kilander, LenaKinhult Ståhlbom, AnneKivipelto, MiiaKoivisto, AnneKornhuber, JohannesKosmidis, Mary H.Kukull, Walter A.Kuksa, Pavel P.Kunkle, Brian W.Kuzma, Amanda B.Lage, CarmenLaukka, Erika J.Launer, LenoreLauria, AlessandraLee, Chien-YuehLehtisalo, JenniLerch, OndrejLleó, AlbertoLongstreth, William, Jr.Lopez, OscarLopez de Munain, AdolfoLove, SethLöwemark, MalinLuckcuck, LaurenLunetta, Kathryn L.Ma, YiyiMacías, JuanMacLeod, Catherine A.Maier, WolfgangMangialasche, FrancescaSpallazzi, MarcoMarquié, MartaMarshall, RachelMartin, Eden R.Martín Montes, AngelMartínez Rodríguez, CarmenMasullo, CarloMayeux, RichardMead, SimonMecocci, PatriziaMedina, MiguelMeggy, AlunMehrabian, ShimaMendoza, SilviaMenéndez-González, ManuelMir, PabloMoebus, SusanneMol, MerelMolina-Porcel, LauraMontrreal, LauraMorelli, LauraMoreno, FerminMorgan, KevinMosley, ThomasNöthen, Markus M.Muchnik, CarolinaMukherjee, ShubhabrataNacmias, BenedettaNgandu, TiiaNicolas, GaelNordestgaard, Børge G.Olaso, RobertOrellana, AdelinaOrsini, MichelaOrtega, GemmaPadovani, AlessandroPaolo, CaffarraPapenberg, GoranParnetti, LucillaPasquier, FlorencePastor, PauPeloso, GinaPérez-Cordón, AlbaPérez-Tur, JordiPericard, PierrePeters, OliverPijnenburg, Yolande A. L.Pineda, Juan A.Piñol-Ripoll, GerardPisanu, ClaudiaPolak, ThomasPopp, JuliusPosthuma, DaniellePriller, JosefPuerta, RaquelQuenez, OlivierQuintela, InésQvist Thomassen, JesperRábano, AlbertoRainero, InnocenzoRajabli, FaridRamakers, InezReal, Luis M.Reinders, Marcel J. T.Reitz, ChristianeReyes-Dumeyer, DollyRidge, PerryRiedel-Heller, SteffiRiederer, PeterRoberto, NataliaRodriguez-Rodriguez, EloyRongve, ArvidRosas Allende, IreneRosende-Roca, MaitéeRoyo, Jose LuisRubino, ElisaRujescu, DanSáez, María EugeniaSakka, ParaskeviSaltvedt, IngvildSanabria, ÁngelaSánchez-Arjona, María BernalSanchez-Garcia, FlorentinoSánchez Juan, PascualSánchez-Valle, RaquelSando, Sigrid B.Sarnowski, ChloéSatizabal, Claudia L.Scamosci, MichelaScarmeas, NikolaosScarpini, ElioScheltens, PhilipScherbaum, NorbertScherer, MartinSchmid, MatthiasSchneider, AnjaSchott, Jonathan M.Selbæk, GeirSeripa, DavideSerrano, ManuelSha, JinShadrin, Alexey A.Skrobot, OliviaSlifer, SusanSnijders, Gijsje J. L.Soininen, HilkkaSolfrizzi, VincenzoSolomon, AlinaSong, YeunjooSorbi, SandroSotolongo-Grau, OscarSpalletta, GianfrancoSpottke, AnnikaSquassina, AlessioStordal, EysteinTartan, Juan PabloTárraga, LluísTesí, NiccoloThalamuthu, AnbupalamThomas, TegosTosto, GiuseppeTraykov, LatchezarTremolizzo, LucioTybjærg-Hansen, AnneUitterlinden, AndreUllgren, AbbeUlstein, IngunValero, SergiValladares, OttoVan Broeckhoven, ChristineVance, JefferyVardarajan, Badri N.van der Lugt, AadVan Dongen, Jaspervan Rooij, Jeroenvan Swieten, JohnVandenberghe, RikVerhey, FransVidal, Jean-SébastienVogelgsang, JonathanVyhnalek, MartinWagner, MichaelWallon, DavidWang, Li-SanWang, RuiqiWeinhold, LeonieWiltfang, JensWindle, GillWoods, BobYannakoulia, MaryZare, HabilZhao, YiZhang, XiaolingZhu, CongcongZulaica, MirenEADBGR@ACEDEGESCOEADIGERADDemgeneFinnGenADGCCHARGEFarrer, Lindsay A.Psaty, Bruce M.Ghanbari, MohsenRaj, TowfiqueSachdev, PerminderMather, KarenJessen, FrankIkram, M. Arfande Mendonça, AlexandreHort, JakubTsolaki, MagdaPericak-Vance, Margaret A.Amouyel, PhilippeWilliams, JulieFrikke-Schmidt, RuthClarimon, JordiDeleuze, Jean-FrançoisRossi, GiacominaSeshadri, SudhaAndreassen, Ole A.Ingelsson, MartinHiltunen, MikkoSleegers, KristelSchellenberg, Gerard D.van Duijn, Cornelia M.Sims, Rebeccavan der Flier, Wiesje M.Ruiz, AgustínRamirez, AlfredoLambert, Jean-Charles2024-05-062024-05-062022Bellenguez 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-zhttps://hdl.handle.net/1805/40501Characterization 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.en-USAttribution 4.0 InternationalAlzheimer's diseaseGenome-wide association studiesCognitive dysfunctionArticle