Arking, Dan EDan EArkingPulit, Sara LSara LPulitCrotti, LiaLiaCrottivan der Harst, PimPimvan der HarstMunroe, Patricia BPatricia BMunroeKoopmann, Tamara TTamara TKoopmannSotoodehnia, NonaNonaSotoodehniaRossin, Elizabeth JElizabeth JRossinMorley, MichaelMichaelMorleyWang, XinchenXinchenWangJohnson, Andrew DAndrew DJohnsonLundby, AliciaAliciaLundbyGudbjartsson, Daníel FDaníel FGudbjartssonNoseworthy, Peter APeter ANoseworthyEijgelsheim, MarkMarkEijgelsheimBradford, YukiYukiBradfordTarasov, Kirill VKirill VTarasovDörr, MarcusMarcusDörrMüller-Nurasyid, MartinaMartinaMüller-NurasyidLahtinen, Annukka MAnnukka MLahtinenNolte, Ilja MIlja MNolteSmith, Albert VernonAlbert VernonSmithBis, Joshua CJoshua CBisIsaacs, AaronAaronIsaacsNewhouse, Stephen JStephen JNewhouseEvans, Daniel SDaniel SEvansPost, Wendy SWendy SPostWaggott, DarylDarylWaggottLyytikäinen, Leo-PekkaLeo-PekkaLyytikäinenHicks, Andrew AAndrew AHicksEisele, LewinLewinEiseleEllinghaus, DavidDavidEllinghausHayward, 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MWittemanKedenko, LyudmylaLyudmylaKedenkoLamina, ClaudiaClaudiaLaminaOostra, Ben ABen AOostraAbecasis, Gonçalo RGonçalo RAbecasisLakatta, Edward GEdward GLakattaMulas, AntonellaAntonellaMulasOrrú, MarcoMarcoOrrúSchlessinger, DavidDavidSchlessingerUda, ManuelaManuelaUdaMarkus, Marcello R PMarcello R PMarkusVölker, UweUweVölkerSnieder, HaroldHaroldSniederSpector, Timothy DTimothy DSpectorÄrnlöv, JohanJohanÄrnlövLind, LarsLarsLindSundström, JohanJohanSundströmSyvänen, Ann-ChristineAnn-ChristineSyvänenKivimaki, MikaMikaKivimakiKähönen, MikaMikaKähönenMononen, NinaNinaMononenRaitakari, Olli TOlli TRaitakariViikari, Jorma SJorma SViikariAdamkova, VeraVeraAdamkovaKiechl, StefanStefanKiechlBrion, MariaMariaBrionNicolaides, Andrew NAndrew NNicolaidesPaulweber, BernhardBernhardPaulweberHaerting, JohannesJohannesHaertingDominiczak, Anna FAnna FDominiczakNyberg, FredrikFredrikNybergWhincup, Peter HPeter HWhincupHingorani, Aroon DAroon DHingoraniSchott, Jean-JacquesJean-JacquesSchottBezzina, Connie RConnie RBezzinaIngelsson, ErikErikIngelssonFerrucci, LuigiLuigiFerrucciGasparini, PaoloPaoloGaspariniWilson, James FJames FWilsonRudan, IgorIgorRudanFranke, AndreAndreFrankeMühleisen, Thomas WThomas WMühleisenPramstaller, Peter PPeter PPramstallerLehtimäki, Terho JTerho JLehtimäkiPaterson, Andrew DAndrew DPatersonParsa, AfshinAfshinParsaLiu, YongmeiYongmeiLiuvan Duijn, Cornelia MCornelia Mvan DuijnSiscovick, David SDavid SSiscovickGudnason, VilmundurVilmundurGudnasonJamshidi, YaldaYaldaJamshidiSalomaa, VeikkoVeikkoSalomaaFelix, Stephan BStephan BFelixSanna, SerenaSerenaSannaRitchie, Marylyn DMarylyn DRitchieStricker, Bruno HBruno HStrickerStefansson, KariKariStefanssonBoyer, Laurie ALaurie ABoyerCappola, Thomas PThomas PCappolaOlsen, Jesper VJesper VOlsenLage, KasperKasperLageSchwartz, Peter JPeter JSchwartzKääb, StefanStefanKääbChakravarti, AravindaAravindaChakravartiAckerman, Michael JMichael JAckermanPfeufer, ArneArnePfeuferde Bakker, Paul I WPaul I Wde BakkerNewton-Cheh, ChristopherChristopherNewton-Cheh2024-10-232024-10-232014-08https://boris-portal.unibe.ch/handle/20.500.12422/129758The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.en600 - Technology::610 - Medicine & health500 - Science::570 - Life sciences; biologyarticle10.7892/boris.638832495274510.1038/ng.3014