Ashar, Foram NForam NAsharMitchell, Rebecca NRebecca NMitchellAlbert, Christine MChristine MAlbertNewton-Cheh, ChristopherChristopherNewton-ChehBrody, Jennifer AJennifer ABrodyMüller-Nurasyid, MartinaMartinaMüller-NurasyidMoes, AnnaAnnaMoesMeitinger, ThomasThomasMeitingerMak, AngelAngelMakHuikuri, HeikkiHeikkiHuikuriJunttila, M JuhaniM JuhaniJunttilaGoyette, PhilippePhilippeGoyettePulit, Sara LSara LPulitPazoki, RahaRahaPazokiTanck, Michael WMichael WTanckBlom, Marieke TMarieke TBlomZhao, XiaoQingXiaoQingZhaoHavulinna, Aki SAki SHavulinnaJabbari, RezaRezaJabbariGlinge, CharlotteCharlotteGlingeTragante, ViniciusViniciusTraganteEscher, Stefan AStefan AEscherChakravarti, AravindaAravindaChakravartiEhret, GeorgGeorgEhretCoresh, JosefJosefCoreshLi, ManManLiPrineas, Ronald JRonald JPrineasFranco Duran, Oscar HoracioOscar HoracioFranco DuranKwok, Pui-YanPui-YanKwokLumley, ThomasThomasLumleyDumas, FlorenceFlorenceDumasMcKnight, BarbaraBarbaraMcKnightRotter, Jerome IJerome IRotterLemaitre, Rozenn NRozenn NLemaitreHeckbert, Susan RSusan RHeckbertO'Donnell, Christopher JChristopher JO'DonnellHwang, Shih-JenShih-JenHwangTardif, Jean-ClaudeJean-ClaudeTardifVanDenburgh, MartinMartinVanDenburghUitterlinden, André GAndré GUitterlindenHofman, AlbertAlbertHofmanStricker, Bruno H CBruno H CStrickerde Bakker, Paul I WPaul I Wde BakkerFranks, Paul WPaul WFranksJansson, Jan-HakanJan-HakanJanssonAsselbergs, Folkert WFolkert WAsselbergsHalushka, Marc KMarc KHalushkaMaleszewski, Joseph JJoseph JMaleszewskiTfelt-Hansen, JacobJacobTfelt-HansenEngstrøm, ThomasThomasEngstrømSalomaa, VeikkoVeikkoSalomaaVirmani, RenuRenuVirmaniKolodgie, FrankFrankKolodgieWilde, Arthur A MArthur A MWildeTan, Hanno LHanno LTanBezzina, Connie RConnie RBezzinaEijgelsheim, MarkMarkEijgelsheimRioux, John DJohn DRiouxJouven, XavierXavierJouvenKääb, StefanStefanKääbPsaty, Bruce MBruce MPsatySiscovick, David SDavid SSiscovickArking, Dan EDan EArkingSotoodehnia, NonaNonaSotoodehniaof the CHARGE Consortium, the SCD working groupthe SCD working groupof the CHARGE Consortium2024-10-252024-10-252018-11-21https://boris-portal.unibe.ch/handle/20.500.12422/164201Aims Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA. Methods and results We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk. Conclusions Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.en600 - Technology::610 - Medicine & health300 - Social sciences, sociology & anthropology::360 - Social problems & social servicesarticle10.7892/boris.1198593016965710.1093/eurheartj/ehy474