Young, William JWilliam JYoungLahrouchi, NajimNajimLahrouchiIsaacs, AaronAaronIsaacsDuong, ThuyVyThuyVyDuongFoco, LuisaLuisaFocoAhmed, FarahFarahAhmedBrody, Jennifer AJennifer ABrodySalman, ReemReemSalmanNoordam, RaymondRaymondNoordamBenjamins, Jan-WalterJan-WalterBenjaminsHaessler, JeffreyJeffreyHaesslerLyytikäinen, Leo-PekkaLeo-PekkaLyytikäinenRepetto, LindaLindaRepettoConcas, Maria PinaMaria PinaConcasvan den Berg, Marten EMarten Evan den BergWeiss, StefanStefanWeissBaldassari, Antoine RAntoine RBaldassariBartz, Traci MTraci MBartzCook, James PJames PCookEvans, Daniel SDaniel SEvansFreudling, RebeccaRebeccaFreudlingHines, OliverOliverHinesIsaksen, Jonas LJonas LIsaksenLin, HonghuangHonghuangLinMei, HaoHaoMeiMoscati, ArdenArdenMoscatiMüller-Nurasyid, MartinaMartinaMüller-NurasyidNursyifa, CasiaCasiaNursyifaQian, YongYongQianRichmond, AnneAnneRichmondRoselli, CarolinaCarolinaRoselliRyan, Kathleen AKathleen ARyanTarazona-Santos, EduardoEduardoTarazona-SantosThériault, SébastienSébastienThériaultvan Duijvenboden, StefanStefanvan DuijvenbodenWarren, Helen RHelen RWarrenYao, JieJieYaoRaza, DaniaDaniaRazaAeschbacher, StefanieStefanieAeschbacherAhlberg, GustavGustavAhlbergAlonso, AlvaroAlvaroAlonsoAndreasen, LauraLauraAndreasenBis, Joshua CJoshua CBisBoerwinkle, EricEricBoerwinkleCampbell, ArchieArchieCampbellCatamo, EulaliaEulaliaCatamoCocca, MassimilianoMassimilianoCoccaCutler, Michael JMichael JCutlerDarbar, DawoodDawoodDarbarDe Grandi, AlessandroAlessandroDe GrandiDe Luca, AntonioAntonioDe LucaDing, JunJunDingEllervik, ChristinaChristinaEllervikEllinor, Patrick TPatrick TEllinorFelix, Stephan BStephan BFelixFroguel, PhilippePhilippeFroguelFuchsberger, ChristianChristianFuchsbergerGögele, MartinMartinGögeleGraff, ClausClausGraffGraff, MariaelisaMariaelisaGraffGuo, XiuqingXiuqingGuoHansen, TorbenTorbenHansenHeckbert, Susan RSusan RHeckbertHuang, Paul LPaul LHuangHuikuri, Heikki VHeikki VHuikuriHutri-Kähönen, NinaNinaHutri-KähönenIkram, M ArfanM ArfanIkramJackson, Rebecca DRebecca DJacksonJunttila, JuhaniJuhaniJunttilaKavousi, MaryamMaryamKavousiKors, Jan AJan AKorsLeal, Thiago PThiago PLealLemaitre, Rozenn NRozenn NLemaitreLin, Henry JHenry JLinLind, LarsLarsLindLinneberg, AllanAllanLinnebergLiu, SiminSiminLiuMacFarlane, Peter WPeter WMacFarlaneMangino, MassimoMassimoManginoMeitinger, ThomasThomasMeitingerMezzavilla, MassimoMassimoMezzavillaMishra, Pashupati PPashupati PMishraMitchell, Rebecca NRebecca NMitchellMononen, NinaNinaMononenMontasser, May EMay EMontasserMorrison, Alanna CAlanna CMorrisonNauck, MatthiasMatthiasNauckNauffal, VictorVictorNauffalNavarro, PauPauNavarroNikus, KjellKjellNikusPare, GuillaumeGuillaumeParePatton, Kristen KKristen KPattonPelliccione, GiuliaGiuliaPelliccionePittman, AlanAlanPittmanPorteous, David JDavid JPorteousPramstaller, Peter PPeter PPramstallerPreuss, Michael HMichael HPreussRaitakari, Olli TOlli TRaitakariReiner, Alexander PAlexander PReinerRibeiro, Antonio Luiz PAntonio Luiz PRibeiroRice, Kenneth MKenneth MRiceRisch, LorenzLorenzRisch0000-0003-2692-6699Schlessinger, DavidDavidSchlessingerSchotten, UlrichUlrichSchottenSchurmann, ClaudiaClaudiaSchurmannShen, XiaXiaShenShoemaker, M BenjaminM BenjaminShoemakerSinagra, GianfrancoGianfrancoSinagraSinner, Moritz FMoritz FSinnerSoliman, Elsayed ZElsayed ZSolimanStoll, MonikaMonikaStollStrauch, KonstantinKonstantinStrauchTarasov, KirillKirillTarasovTaylor, Kent DKent DTaylorTinker, AndrewAndrewTinkerTrompet, StellaStellaTrompetUitterlinden, AndréAndréUitterlindenVölker, UweUweVölkerVölzke, HenryHenryVölzkeWaldenberger, MelanieMelanieWaldenbergerWeng, Lu-ChenLu-ChenWengWhitsel, Eric AEric AWhitselWilson, James GJames GWilsonAvery, Christy LChristy LAveryConen, DavidDavidConenCorrea, AdolfoAdolfoCorreaCucca, FrancescoFrancescoCuccaDörr, MarcusMarcusDörrGharib, Sina ASina AGharibGirotto, GiorgiaGiorgiaGirottoGrarup, NielsNielsGrarupHayward, CarolineCarolineHaywardJamshidi, YaldaYaldaJamshidiJärvelin, Marjo-RiittaMarjo-RiittaJärvelinJukema, J WouterJ WouterJukemaKääb, StefanStefanKääbKähönen, MikaMikaKähönenKanters, Jørgen KJørgen KKantersKooperberg, CharlesCharlesKooperbergLehtimäki, TerhoTerhoLehtimäkiLima-Costa, Maria FernandaMaria FernandaLima-CostaLiu, YongmeiYongmeiLiuLoos, Ruth J FRuth J FLoosLubitz, Steven ASteven ALubitzMook-Kanamori, Dennis ODennis OMook-KanamoriMorris, Andrew PAndrew PMorrisO'Connell, Jeffrey RJeffrey RO'ConnellOlesen, Morten SallingMorten SallingOlesenOrini, MicheleMicheleOriniPadmanabhan, SandoshSandoshPadmanabhanPattaro, CristianCristianPattaroPeters, AnnetteAnnettePetersPsaty, Bruce MBruce MPsatyRotter, Jerome IJerome IRotterStricker, BrunoBrunoStrickervan der Harst, PimPimvan der Harstvan Duijn, Cornelia MCornelia Mvan DuijnVerweij, NiekNiekVerweijWilson, James FJames FWilsonArking, Dan EDan EArkingRamirez, JuliaJuliaRamirezLambiase, Pier DPier DLambiaseSotoodehnia, NonaNonaSotoodehniaMifsud, BorbalaBorbalaMifsudNewton-Cheh, ChristopherChristopherNewton-ChehMunroe, Patricia BPatricia BMunroe2024-10-112024-10-112022-09-01https://boris-portal.unibe.ch/handle/20.500.12422/87228The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.en600 - Technology::610 - Medicine & healtharticle10.48350/1726573605032110.1038/s41467-022-32821-z