Bellenguez, CélineKüçükali, FahriJansen, Iris EKleineidam, LucaMoreno-Grau, SoniaAmin, NajafNaj, Adam CCampos-Martin, RafaelGrenier-Boley, BenjaminAndrade, VictorHolmans, Peter ABoland, AnneDamotte, Vincentvan der Lee, Sven JCosta, Marcos RKuulasmaa, TeemuYang, Qiongde Rojas, ItziarBis, Joshua CYaqub, AmberProkic, IvanaChapuis, JulienAhmad, ShahzadGiedraitis, VilmantasAarsland, DagGarcia-Gonzalez, PabloAbdelnour, CarlaAlarcón-Martín, EmilioAlcolea, DanielAlegret, MontserratAlvarez, IgnacioÁlvarez, VictoriaArmstrong, Nicola JTsolaki, AnthoulaAntúnez, CarmenAppollonio, IldebrandoArcaro, MarinaArchetti, SilvanaPastor, Alfonso AriasArosio, BeatriceAthanasiu, LaviniaBailly, HenriBanaj, NerisaBaquero, MiquelBarral, SandraBeiser, AlexaPastor, Ana BelénBelow, Jennifer EBenchek, PenelopeBenussi, LuisaBerr, ClaudineBesse, CélineBessi, ValentinaBinetti, GiulianoBizarro, AlessandraBlesa, RafaelBoada, MercèBoerwinkle, EricBorroni, BarbaraBoschi, SilviaBossù, PaolaBråthen, GeirBressler, JanBresner, 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MMuchnik, CarolinaMukherjee, ShubhabrataNacmias, BenedettaNgandu, TiiaNicolas, GaelNordestgaard, Børge GOlaso, RobertOrellana, AdelinaOrsini, MichelaOrtega, GemmaPadovani, AlessandroPaolo, CaffarraPapenberg, GoranParnetti, LucillaPasquier, FlorencePastor, PauPeloso, GinaPérez-Cordón, AlbaPérez-Tur, JordiPericard, PierrePeters, OliverPijnenburg, Yolande A LPineda, Juan APiñol-Ripoll, GerardPisanu, ClaudiaPolak, ThomasPopp, JuliusPosthuma, DaniellePriller, JosefPuerta, RaquelQuenez, OlivierQuintela, InésThomassen, Jesper QvistRábano, AlbertoRainero, InnocenzoRajabli, FaridRamakers, InezReal, Luis MReinders, Marcel J TReitz, ChristianeReyes-Dumeyer, DollyRidge, PerryRiedel-Heller, SteffiRiederer, PeterRoberto, NataliaRodriguez-Rodriguez, EloyRongve, ArvidAllende, Irene RosasRosende-Roca, MaitéeRoyo, Jose LuisRubino, ElisaRujescu, DanSáez, María EugeniaSakka, ParaskeviSaltvedt, IngvildSanabria, ÁngelaSánchez-Arjona, María BernalSanchez-Garcia, FlorentinoJuan, Pascual SánchezSánchez-Valle, RaquelSando, Sigrid BSarnowski, ChloéSatizabal, Claudia LScamosci, MichelaScarmeas, NikolaosScarpini, ElioScheltens, PhilipScherbaum, NorbertScherer, MartinSchmid, MatthiasSchneider, AnjaSchott, Jonathan MSelbæk, GeirSeripa, DavideSerrano, ManuelSha, JinShadrin, Alexey ASkrobot, OliviaSlifer, SusanSnijders, Gijsje J LSoininen, 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, OttoBroeckhoven, Christine VanVance, JefferyVardarajan, Badri Nvan der Lugt, AadDongen, Jasper Vanvan 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 APsaty, Bruce MGhanbari, MohsenRaj, TowfiqueSachdev, PerminderMather, KarenJessen, FrankIkram, M Arfande Mendonça, AlexandreHort, JakubTsolaki, MagdaPericak-Vance, Margaret AAmouyel, PhilippeWilliams, JulieFrikke-Schmidt, RuthClarimon, JordiDeleuze, Jean-FrançoisRossi, GiacominaSeshadri, SudhaAndreassen, Ole AIngelsson, MartinHiltunen, MikkoSleegers, KristelSchellenberg, Gerard Dvan Duijn, Cornelia MSims, Rebeccavan der Flier, Wiesje MRuiz, AgustínRamirez, AlfredoLambert, Jean-Charles2023-05-032023-05-032022-04-04http://hdl.handle.net/10668/19571Characterization 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Alzheimer DiseaseCognitive DysfunctionGenome-Wide Association StudyHumanstau Proteinsresearch article35379992open access10.1038/s41588-022-01024-z1546-1718PMC9005347https://www.nature.com/articles/s41588-022-01024-z.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005347/pdf