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Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Itziar De RojasSonia Moreno-GrauNiccolo TesiBenjamin Grenier-BoleyVictor AndradeIris E JansenNancy L PedersenNajada StringaAnna ZettergrenIsabel HernándezLaura MontrrealCarmen AntúnezAnna AntonellRick M TankardJoshua C BisRebecca SimsCeline BellenguezInés QuintelaAntonio González-PerezMiguel Calero LaraEmilio Franco-MacíasJuan MacíasRafael BlesaLaura Cervera-CarlesMenéndez-González ManuelAna Frank-GarcíaJose Luís RoyoFermin MorenoRaquel Huerto VilasMiquel BaqueroMónica Diez-FairenCarmen LageSebastián García-MadronaPablo García GonzálezEmilio Alarcón-MartínSergi ValeroOscar Sotolongo-GrauAbbe UllgrenAdam C NajAfina W LemstraAlba BenaqueAlba Pérez-CordónAlberto BenussiAlberto RábanoAlessandro PadovaniAlessio SquassinaAlexandre de MendonçaAlfonso Arias PastorAlmar A L KokAlun MeggyAna Belén PastorAna EspinosaAnaïs Corma-GómezAngel Martín MontesÁngela SanabriaAnita L DeStefanoAnja SchneiderAnnakaisa HaapasaloAnne Kinhult StåhlbomAnne Tybjærg-HansenAnnette M HartmannAnnika SpottkeArturo Corbatón-AnchueloArvid RongveBarbara BorroniBeatrice ArosioBenedetta NacmiasBørge Grønne NordestgaardBrian W KunkleCamille CharbonnierCarla AbdelnourCarlo MasulloCarmen Martínez RodríguezCarmen Muñoz-FernandezCarole DufouilCaroline GraffCatarina B FerreiraCaterina ChillottiChandra A ReynoldsChiara FenoglioChristine Van BroeckhovenChristopher ClarkClaudia PisanuClaudia L SatizabalClive HolmesDolores Buiza-RuedaDag AarslandDan RujescuDaniel AlcoleaDaniela GalimbertiDavid WallonDavide SeripaEdna GrünblattEfthimios DardiotisEmrah DüzelElio ScarpiniElisa ContiElisa RubinoEllen GelpiEloy Rodríguez-RodríguezEmmanuelle DuronEric BoerwinkleEvelyn FerriFabrizio TagliaviniFahri KüçükaliFlorence PasquierFlorentino Sanchez-GarciaFrancesca MangialascheFrank JessenGaël NicolasGeir SelbaekGemma OrtegaGeneviève ChêneGeorgios HadjigeorgiouGiacomina RossiGianfranco SpallettaGiorgio GiacconeGiulia GrandeGiuliano BinettiGoran PapenbergHarald HampelHenri BaillyHenrik ZetterbergHilkka SoininenIda K KarlssonIgnacio AlvarezIldebrando AppollonioIna GieglingIngmar SkoogIngvild SaltvedtInnocenzo RaineroIrene Rosas AllendeJakub HortJanine Diehl-SchmidJasper Van DongenJean-Sébastien VidalJenni LehtisaloJens WiltfangJesper Qvist ThomassenKornhuber JohannesJonathan L HainesJonathan S VogelgsangJuan Antonio PinedaJuan ForteaJulius PoppJürgen DeckertKatharina BuergerKevin MorganKlaus FließbachKristel SleegersLaura Molina-PorcelLena KilanderLeonie WeinholdLindsay A FarrerLi-San WangLuca KleineidamLucia FarottiLucilla ParnettiLucio TremolizzoLucrezia HausnerLuisa BenussiLutz FroelichMohammad Arfan IkramM Candida Deniz-NaranjoMagdalini TsolakiMaitée Rosende-RocaMalin LöwenmarkMarc HulsmanMarco SpallazziMargaret A Pericak-VanceMargaret EsiriMaría Bernal Sánchez-ArjonaMaria Carolina DalmassoMaría Teresa Martínez-LarradMarina ArcaroMarkus M NöthenMarta Fernández-FuertesMartin DichgansMartin IngelssonMartin J HerrmannMartin SchererMartin VyhnalekMary H KosmidisMary YannakouliaMatthias SchmidMichael EwersMichael T HenekaMichael WagnerMichela ScamosciMiia KivipeltoMikko HiltunenMiren ZulaicaMontserrat AlegretMyriam FornageNatalia RobertoNatasja M van SchoorNazib M SeiduNerisa BanajNicola J ArmstrongNikolaos ScarmeasNorbert ScherbaumOliver GoldhardtOliver HanonOliver PetersOlivia Anna SkrobotOlivier QuenezOndrej LerchPaola BossùPaolo CaffarraPaolo Dionigi RossiParaskevi SakkaPer HoffmannPeter A HolmansPeter FischerPeter RiedererQiong YangRachel MarshallRajesh N KalariaRichard MayeuxRik VandenbergheRoberta CecchettiRoberta GhidoniRuth Frikke-SchmidtSandro SorbiSara HäggSebastiaan EngelborghsSeppo HelisalmiSigrid Botne SandoSilke KernSilvana ArchettiSilvia BoschiSilvia FostinelliSilvia GilSilvia MendozaSimon MeadSimona CicconeSrdjan DjurovicStefanie Heilmann-HeimbachSteffi Riedel-HellerTeemu KuulasmaaTeodoro Del SerThibaud LebouvierThomas PolakTiia NganduTimo GrimmerValentina BessiValentina Escott-PriceVilmantas GiedraitisVincent DeramecourtWolfgang MaierXueqiu JianYolande A L Pijnenburgnull nullnull nullnull nullnull nullnull nullPatrick Gavin KehoeGuillermo Garcia-RibasPascual Sánchez JuanPau PastorJordi Pérez TurGerard Piñol-RipollAdolfo Lopez de MunainJose Maria García-AlbercaMaria Jesus BullidoVictoria ÁlvarezAlberto LleóLuis Miguel RealPablo MirMiguel Medina PadillaPhilip ScheltensHenne HolstegeMarta MarquiéMaría Eugenia SáezÁngel CarracedoPhillippe AmouyelGerard D SchellenbergJulie WilliamsSudha SeshadriCornelia M Van DuijnKaren A MatherRaquel Sánchez-ValleManuel Serrano-RíosAdelina OrellanaLluís TárragaKaj BlennowMartijn HuismanOle Andreas AndreassenDanielle PosthumaJordi ClarimónMerce BoadaWiesje Maria van der FlierAlfredo RamirezJean-Charles LambertSven J Van der LeeAgustin Ruiz
Published in: Nature communications (2021)
Genetic 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.
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