de-Rojas, ItziarMoreno-Grau, SoniaTesi, NiccoloGrenier-Boley, BenjaminAndrade, VictorJansen, Iris EPedersen, Nancy LStringa, NajadaZettergren, AnnaHernández, IsabelMontrreal, LauraAntúnez, CarmenAntonell, AnnaTankard, Rick MBis, Joshua CSims, RebeccaBellenguez, CélineQuintela, InésGonzález-Perez, AntonioCalero, MiguelFranco-Macias, EmilioMacias, JuanBlesa, RafaelCervera-Carles, LauraMenendez-Gonzalez, ManuelFrank-Garcia, AnaRoyo, Jose LuisMoreno, FerminHuerto-Vilas, RaquelBaquero, MiquelDiez-Fairen, MonicaLage, CarmenGarcia-Madrona, SebastianGarcia-Gonzalez, PabloAlarcon-Martin, EmilioValero, SergiSotolongo-Grau, OscarUllgren, AbbeNaj, Adam CLemstra, Afina WBenaque, AlbaPerez-Cordon, AlbaBenussi, AlbertoRabano, AlbertoPadovani, AlessandroSquassina, Alessiode-Mendonça, AlexandreArias-Pastor, AlfonsoKok, Almar A LMeggy, AlunPastor, Ana BelenEspinosa, AnaCorma-Gomez, AnaïsMartin-Montes, AngelSanabria, AngelaDeStefano, Anita LSchneider, AnjaHaapasalo, AnnakaisaKinhult-Ståhlbom, AnneTybjærg-Hansen, AnneHartmann, Annette MSpottke, AnnikaCorbaton-Anchuelo, ArturoRongve, ArvidBorroni, BarbaraArosio, BeatriceNacmias, BenedettaNordestgaard, Børge GKunkle, Brian WCharbonnier, CamilleAbdelnour, CarlaMasullo, CarloMartinez-Rodriguez, CarmenMuñoz-Fernandez, CarmenDufouil, CaroleGraff, CarolineFerreira, Catarina BChillotti, CaterinaReynolds, Chandra AFenoglio, ChiaraVan-Broeckhoven, ChristineClark, ChristopherPisanu, ClaudiaSatizabal, Claudia LHolmes, CliveBuiza-Rueda, DoloresAarsland, DagRujescu, DanAlcolea, DanielGalimberti, DanielaWallon, DavidSeripa, DavideGrünblatt, EdnaDardiotis, EfthimiosDüzel, EmrahScarpini, ElioConti, ElisaRubino, ElisaGelpi, EllenRodriguez-Rodriguez, EloyDuron, EmmanuelleBoerwinkle, EricFerri, EvelynTagliavini, FabrizioKüçükali, FahriPasquier, FlorenceSanchez-Garcia, FlorentinoMangialasche, FrancescaJessen, FrankNicolas, GaëlSelbæk, GeirOrtega, GemmaChêne, GenevièveHadjigeorgiou, GeorgiosRossi, GiacominaSpalletta, GianfrancoGiaccone, GiorgioGrande, GiuliaBinetti, GiulianoPapenberg, GoranHampel, HaraldBailly, HenriZetterberg, HenrikSoininen, HilkkaKarlsson, Ida KAlvarez, IgnacioAppollonio, IldebrandoGiegling, InaSkoog, IngmarSaltvedt, IngvildRainero, InnocenzoRosas-Allende, IreneHort, JakubDiehl-Schmid, JanineVan-Dongen, JasperVidal, Jean-SebastienLehtisalo, JenniWiltfang, JensThomassen, Jesper QvistKornhuber, JohannesHaines, Jonathan LVogelgsang, JonathanPineda, Juan AFortea, JuanPopp, JuliusDeckert, JürgenBuerger, KatharinaMorgan, KevinFließbach, KlausSleegers, KristelMolina-Porcel, LauraKilander, LenaWeinhold, LeonieFarrer, Lindsay AWang, Li-SanKleineidam, LucaFarotti, LuciaParnetti, LucillaTremolizzo, LucioHausner, LucreziaBenussi, LuisaFroelich, LutzIkram, M ArfanDeniz-Naranjo, M CandidaTsolaki, MagdaRosende-Roca, MaiteeLöwenmark, MalinHulsman, MarcSpallazzi, MarcoPericak-Vance, Margaret AEsiri, MargaretBernal-Sanchez-Arjona, MariaDalmasso, Maria CarolinaMartinez-Larrad, Maria TeresaArcaro, MarinaNöthen, Markus MFernandez-Fuertes, MartaDichgans, MartinIngelsson, MartinHerrmann, Martin JScherer, MartinVyhnalek, MartinKosmidis, Mary HYannakoulia, MarySchmid, MatthiasEwers, MichaelHeneka, Michael TWagner, MichaelScamosci, MichelaKivipelto, MiiaHiltunen, MikkoZulaica, MirenAlegret, MontserratFornage, MyriamRoberto, Nataliavan-Schoor, Natasja MSeidu, Nazib MBanaj, NerisaArmstrong, Nicola JScarmeas, NikolaosScherbaum, NorbertGoldhardt, OliverHanon, OliverPeters, OliverSkrobot, Olivia AnnaQuenez, OlivierLerch, OndrejBossu, PaolaCaffarra, PaoloDionigi-Rossi, PaoloSakka, ParaskeviMecocci, PatriziaHoffmann, PerHolmans, Peter AFischer, PeterRiederer, PeterYang, QiongMarshall, RachelKalaria, Rajesh NMayeux, RichardVandenberghe, RikCecchetti, RobertaGhidoni, RobertaFrikke-Schmidt, RuthSorbi, SandroHägg, SaraEngelborghs, SebastiaanHelisalmi, SeppoBotne-Sando, SigridKern, SilkeArchetti, SilvanaBoschi, SilviaFostinelli, SilviaGil, SilviaMendoza, SilviaMead, SimonCiccone, SimonaDjurovic, SrdjanHeilmann-Heimbach, StefanieRiedel-Heller, SteffiKuulasmaa, TeemuDel Ser, TeodoroLebouvier, ThibaudPolak, ThomasNgandu, TiiaGrimmer, TimoBessi, ValentinaEscott-Price, ValentinaGiedraitis, VilmantasDeramecourt, VincentMaier, WolfgangJian, XueqiuPijnenburg, Yolande A LKehoe, Patrick GavinGarcia-Ribas, GuillermoSanchez-Juan, PascualPastor, PauPerez-Tur, JordiPiñol-Ripoll, GerardLopez-de-Munain, AdolfoGarcia-Alberca, Jose MariaBullido, Maria JAlvarez, VictoriaLleo, AlbertoReal, Luis MMir, PabloMedina, MiguelScheltens, PhilipHolstege, HenneMarquie, MartaSaez, Maria EugeniaCarracedo, AngelAmouyel, PhilippeSchellenberg, Gerard DWilliams, JulieSeshadri, Sudhavan-Duijn, Cornelia MMather, Karen ASanchez-Valle, RaquelSerrano-Rios, ManuelOrellana, AdelinaTarraga, LluisBlennow, KajHuisman, MartijnAndreassen, Ole APosthuma, DanielleClarimon, JordiBoada, Mercevan-der-Flier, Wiesje MRamirez, AlfredoLambert, Jean-Charlesvan-der-Lee, Sven JRuiz, Agustin2025-01-072025-01-072021-06-07de Rojas I, Moreno-Grau S, Tesi N, Grenier-Boley B, Andrade V, Jansen IE, et al. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores. Nat Commun. 2021 Jun 7;12(1):3417.https://hdl.handle.net/10668/27256Genetic 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Age of OnsetAlzheimer DiseaseApolipoproteins EDatasets as TopicGenetic Predisposition to DiseaseGenome-Wide Association StudyMalePolymorphism, Single NucleotideRisk FactorsAgedAged, 80 and overAmyloid beta-Protein PrecursorCase-Control StudiesCohort StudiesFemaleFollow-Up StudiesHeterozygoteHumansMiddle AgedMultifactorial InheritanceRisk Assessmentresearch article34099642open accessEnfermedad de AlzheimerPuntuación de riesgo genéticoApolipoproteínas EComprensiónAmiloideEstudios de asociación genéticaApoderadoConductores10.1038/s41467-021-22491-82041-1723PMC8184987https://www.nature.com/articles/s41467-021-22491-8.pdfhttps://pmc.ncbi.nlm.nih.gov/articles/PMC8184987/pdf