10059nas a2203157 4500008004100000022001400041245012200055210006900177260001300246300001100259490000700270520116100277653001001438653000901448653002501457653002201482653002701504653002401531653001101555653003801566653003401604653001301638653002101651653001101672653002101683653000901704653001601713653001501729653003601744100001901780700001901799700001601818700001501834700002401849700002401873700002201897700002501919700002001944700001801964700002301982700001902005700002802024700002502052700002202077700001902099700002302118700001802141700003002159700002502189700001902214700002602233700001902259700001802278700002502296700002102321700001902342700001902361700002802380700002102408700001802429700002202447700002202469700001702491700001802508700002002526700002102546700002302567700002302590700001802613700002302631700002002654700002502674700002302699700002302722700002602745700001802771700002202789700002502811700002302836700002502859700002102884700002202905700002202927700002302949700001902972700001902991700001703010700002003027700002003047700002103067700002503088700001803113700002303131700002203154700002403176700002003200700001803220700002203238700003903260700001703299700002103316700002203337700002303359700002003382700002203402700001803424700001903442700002003461700001903481700001803500700002003518700001603538700002803554700002103582700001803603700002303621700002003644700002103664700002203685700003003707700001703737700001703754700002203771700002103793700002403814700002103838700002403859700002203883700001603905700002203921700002203943700002103965700001903986700001904005700001904024700001804043700002404061700001904085700002304104700002204127700002004149700001904169700002204188700002204210700002004232700002004252700001804272700002204290700002604312700002304338700001704361700003104378700002704409700001804436700002404454700001804478700002304496700002004519700002704539700002404566700003004590700001704620700002004637700002004657700001904677700002104696700002404717700002404741700002504765700002304790700002604813700002604839700002704865700002604892700001604918700002204934700002004956700001904976700002504995700001805020700002705038700002405065700001805089700002905107700002805136700002005164700002205184700002105206700001905227700001705246700002805263700003005291700002205321700002005343700001905363700002505382700002305407700002105430700001705451700002405468700001705492700002605509700001705535700002005552700002405572700001905596700001505615700002205630700002805652700001905680700002005699700001805719700002305737700002205760700001905782700001905801700001705820700002605837700002405863700002305887700002405910700002005934700002205954700002405976700002506000700002306025700002006048700002006068700002106088700002106109700001606130700001806146700002606164700002606190700002506216700002406241700001806265700001706283700002306300700002406323700002406347700002006371700002006391700002206411700001806433700002406451700002306475700002106498700002106519700002306540700002106563700001706584700002306601700001906624700002606643700002506669700001806694700002506712700002906737710002006766710002206786710001406808710002206822710002106844856003606865 2014 eng d a1546-171800aGenetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.0 aGenetic association study of QT interval highlights role for cal c2014 Aug a826-360 v463 a
The 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.
10aAdult10aAged10aArrhythmias, Cardiac10aCalcium Signaling10aDeath, Sudden, Cardiac10aElectrocardiography10aFemale10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aGenotype10aHeart Ventricles10aHumans10aLong QT Syndrome10aMale10aMiddle Aged10aMyocardium10aPolymorphism, Single Nucleotide1 aArking, Dan, E1 aPulit, Sara, L1 aCrotti, Lia1 aHarst, Pim1 aMunroe, Patricia, B1 aKoopmann, Tamara, T1 aSotoodehnia, Nona1 aRossin, Elizabeth, J1 aMorley, Michael1 aWang, Xinchen1 aJohnson, Andrew, D1 aLundby, Alicia1 aGudbjartsson, Daniel, F1 aNoseworthy, Peter, A1 aEijgelsheim, Mark1 aBradford, Yuki1 aTarasov, Kirill, V1 aDörr, Marcus1 aMüller-Nurasyid, Martina1 aLahtinen, Annukka, M1 aNolte, Ilja, M1 aSmith, Albert, Vernon1 aBis, Joshua, C1 aIsaacs, Aaron1 aNewhouse, Stephen, J1 aEvans, Daniel, S1 aPost, Wendy, S1 aWaggott, Daryl1 aLyytikäinen, Leo-Pekka1 aHicks, Andrew, A1 aEisele, Lewin1 aEllinghaus, David1 aHayward, Caroline1 aNavarro, Pau1 aUlivi, Sheila1 aTanaka, Toshiko1 aTester, David, J1 aChatel, Stéphanie1 aGustafsson, Stefan1 aKumari, Meena1 aMorris, Richard, W1 aNaluai, Åsa, T1 aPadmanabhan, Sandosh1 aKluttig, Alexander1 aStrohmer, Bernhard1 aPanayiotou, Andrie, G1 aTorres, Maria1 aKnoflach, Michael1 aHubacek, Jaroslav, A1 aSlowikowski, Kamil1 aRaychaudhuri, Soumya1 aKumar, Runjun, D1 aHarris, Tamara, B1 aLauner, Lenore, J1 aShuldiner, Alan, R1 aAlonso, Alvaro1 aBader, Joel, S1 aEhret, Georg1 aHuang, Hailiang1 aKao, Linda, W H1 aStrait, James, B1 aMacfarlane, Peter, W1 aBrown, Morris1 aCaulfield, Mark, J1 aSamani, Nilesh, J1 aKronenberg, Florian1 aWilleit, Johann1 aSmith, Gustav1 aGreiser, Karin, H1 aSchwabedissen, Henriette, Meyer Zu1 aWerdan, Karl1 aCarella, Massimo1 aZelante, Leopoldo1 aHeckbert, Susan, R1 aPsaty, Bruce, M1 aRotter, Jerome, I1 aKolcic, Ivana1 aPolasek, Ozren1 aWright, Alan, F1 aGriffin, Maura1 aDaly, Mark, J1 aArnar, David, O1 aHolm, Hilma1 aThorsteinsdottir, Unnur1 aDenny, Joshua, C1 aRoden, Dan, M1 aZuvich, Rebecca, L1 aEmilsson, Valur1 aPlump, Andrew, S1 aLarson, Martin, G1 aO'Donnell, Christopher, J1 aYin, Xiaoyan1 aBobbo, Marco1 aD'Adamo, Adamo, P1 aIorio, Annamaria1 aSinagra, Gianfranco1 aCarracedo, Angel1 aCummings, Steven, R1 aNalls, Michael, A1 aJula, Antti1 aKontula, Kimmo, K1 aMarjamaa, Annukka1 aOikarinen, Lasse1 aPerola, Markus1 aPorthan, Kimmo1 aErbel, Raimund1 aHoffmann, Per1 aJöckel, Karl-Heinz1 aKälsch, Hagen1 aNöthen, Markus, M1 aHoed, Marcel, den1 aLoos, Ruth, J F1 aThelle, Dag, S1 aGieger, Christian1 aMeitinger, Thomas1 aPerz, Siegfried1 aPeters, Annette1 aPrucha, Hanna1 aSinner, Moritz, F1 aWaldenberger, Melanie1 ade Boer, Rudolf, A1 aFranke, Lude1 avan der Vleuten, Pieter, A1 aBeckmann, Britt, Maria1 aMartens, Eimo1 aBardai, Abdennasser1 aHofman, Nynke1 aWilde, Arthur, A M1 aBehr, Elijah, R1 aDalageorgou, Chrysoula1 aGiudicessi, John, R1 aMedeiros-Domingo, Argelia1 aBarc, Julien1 aKyndt, Florence1 aProbst, Vincent1 aGhidoni, Alice1 aInsolia, Roberto1 aHamilton, Robert, M1 aScherer, Stephen, W1 aBrandimarto, Jeffrey1 aMargulies, Kenneth1 aMoravec, Christine, E1 aM, Fabiola, del Greco1 aFuchsberger, Christian1 aO'Connell, Jeffrey, R1 aLee, Wai, K1 aWatt, Graham, C M1 aCampbell, Harry1 aWild, Sarah, H1 aMokhtari, Nour, E El1 aFrey, Norbert1 aAsselbergs, Folkert, W1 aLeach, Irene, Mateo1 aNavis, Gerjan1 avan den Berg, Maarten, P1 avan Veldhuisen, Dirk, J1 aKellis, Manolis1 aKrijthe, Bouwe, P1 aFranco, Oscar, H1 aHofman, Albert1 aKors, Jan, A1 aUitterlinden, André, G1 aWitteman, Jacqueline, C M1 aKedenko, Lyudmyla1 aLamina, Claudia1 aOostra, Ben, A1 aAbecasis, Goncalo, R1 aLakatta, Edward, G1 aMulas, Antonella1 aOrrù, Marco1 aSchlessinger, David1 aUda, Manuela1 aMarkus, Marcello, R P1 aVölker, Uwe1 aSnieder, Harold1 aSpector, Timothy, D1 aArnlöv, Johan1 aLind, Lars1 aSundström, Johan1 aSyvänen, Ann-Christine1 aKivimaki, Mika1 aKähönen, Mika1 aMononen, Nina1 aRaitakari, Olli, T1 aViikari, Jorma, S1 aAdamkova, Vera1 aKiechl, Stefan1 aBrion, Maria1 aNicolaides, Andrew, N1 aPaulweber, Bernhard1 aHaerting, Johannes1 aDominiczak, Anna, F1 aNyberg, Fredrik1 aWhincup, Peter, H1 aHingorani, Aroon, D1 aSchott, Jean-Jacques1 aBezzina, Connie, R1 aIngelsson, Erik1 aFerrucci, Luigi1 aGasparini, Paolo1 aWilson, James, F1 aRudan, Igor1 aFranke, Andre1 aMühleisen, Thomas, W1 aPramstaller, Peter, P1 aLehtimäki, Terho, J1 aPaterson, Andrew, D1 aParsa, Afshin1 aLiu, Yongmei1 aDuijn, Cornelia, M1 aSiscovick, David, S1 aGudnason, Vilmundur1 aJamshidi, Yalda1 aSalomaa, Veikko1 aFelix, Stephan, B1 aSanna, Serena1 aRitchie, Marylyn, D1 aStricker, Bruno, H1 aStefansson, Kari1 aBoyer, Laurie, A1 aCappola, Thomas, P1 aOlsen, Jesper, V1 aLage, Kasper1 aSchwartz, Peter, J1 aKääb, Stefan1 aChakravarti, Aravinda1 aAckerman, Michael, J1 aPfeufer, Arne1 ade Bakker, Paul, I W1 aNewton-Cheh, Christopher1 aCARe Consortium1 aCOGENT Consortium1 aDCCT/EDIC1 aeMERGE Consortium1 aHRGEN Consortium uhttps://chs-nhlbi.org/node/654407420nas a2202053 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2016 eng d a1558-359700a52 Genetic Loci Influencing Myocardial Mass.0 a52 Genetic Loci Influencing Myocardial Mass c2016 Sep 27 a1435-480 v683 aBACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.
OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass.
METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment.
RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo.
CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.
1 aHarst, Pim1 avan Setten, Jessica1 aVerweij, Niek1 aVogler, Georg1 aFranke, Lude1 aMaurano, Matthew, T1 aWang, Xinchen1 aLeach, Irene, Mateo1 aEijgelsheim, Mark1 aSotoodehnia, Nona1 aHayward, Caroline1 aSorice, Rossella1 aMeirelles, Osorio1 aLyytikäinen, Leo-Pekka1 aPolasek, Ozren1 aTanaka, Toshiko1 aArking, Dan, E1 aUlivi, Sheila1 aTrompet, Stella1 aMüller-Nurasyid, Martina1 aSmith, Albert, V1 aDörr, Marcus1 aKerr, Kathleen, F1 aMagnani, Jared, W1 aM, Fabiola, del Greco1 aZhang, Weihua1 aNolte, Ilja, M1 aSilva, Claudia, T1 aPadmanabhan, Sandosh1 aTragante, Vinicius1 aEsko, Tõnu1 aAbecasis, Goncalo, R1 aAdriaens, Michiel, E1 aAndersen, Karl1 aBarnett, Phil1 aBis, Joshua, C1 aBodmer, Rolf1 aBuckley, Brendan, M1 aCampbell, Harry1 aCannon, Megan, V1 aChakravarti, Aravinda1 aChen, Lin, Y1 aDelitala, Alessandro1 aDevereux, Richard, B1 aDoevendans, Pieter, A1 aDominiczak, Anna, F1 aFerrucci, Luigi1 aFord, Ian1 aGieger, Christian1 aHarris, Tamara, B1 aHaugen, Eric1 aHeinig, Matthias1 aHernandez, Dena, G1 aHillege, Hans, L1 aHirschhorn, Joel, N1 aHofman, Albert1 aHubner, Norbert1 aHwang, Shih-Jen1 aIorio, Annamaria1 aKähönen, Mika1 aKellis, Manolis1 aKolcic, Ivana1 aKooner, Ishminder, K1 aKooner, Jaspal, S1 aKors, Jan, A1 aLakatta, Edward, G1 aLage, Kasper1 aLauner, Lenore, J1 aLevy, Daniel1 aLundby, Alicia1 aMacfarlane, Peter, W1 aMay, Dalit1 aMeitinger, Thomas1 aMetspalu, Andres1 aNappo, Stefania1 aNaitza, Silvia1 aNeph, Shane1 aNord, Alex, S1 aNutile, Teresa1 aOkin, Peter, M1 aOlsen, Jesper, V1 aOostra, Ben, A1 aPenninger, Josef, M1 aPennacchio, Len, A1 aPers, Tune, H1 aPerz, Siegfried1 aPeters, Annette1 aPinto, Yigal, M1 aPfeufer, Arne1 aPilia, Maria, Grazia1 aPramstaller, Peter, P1 aPrins, Bram, P1 aRaitakari, Olli, T1 aRaychaudhuri, Soumya1 aRice, Ken, M1 aRossin, Elizabeth, J1 aRotter, Jerome, I1 aSchafer, Sebastian1 aSchlessinger, David1 aSchmidt, Carsten, O1 aSehmi, Jobanpreet1 aSilljé, Herman, H W1 aSinagra, Gianfranco1 aSinner, Moritz, F1 aSlowikowski, Kamil1 aSoliman, Elsayed, Z1 aSpector, Timothy, D1 aSpiering, Wilko1 aStamatoyannopoulos, John, A1 aStolk, Ronald, P1 aStrauch, Konstantin1 aTan, Sian-Tsung1 aTarasov, Kirill, V1 aTrinh, Bosco1 aUitterlinden, André, G1 avan den Boogaard, Malou1 aDuijn, Cornelia, M1 aGilst, Wiek, H1 aViikari, Jorma, S1 aVisscher, Peter, M1 aVitart, Veronique1 aVölker, Uwe1 aWaldenberger, Melanie1 aWeichenberger, Christian, X1 aWestra, Harm-Jan1 aWijmenga, Cisca1 aWolffenbuttel, Bruce, H1 aYang, Jian1 aBezzina, Connie, R1 aMunroe, Patricia, B1 aSnieder, Harold1 aWright, Alan, F1 aRudan, Igor1 aBoyer, Laurie, A1 aAsselbergs, Folkert, W1 avan Veldhuisen, Dirk, J1 aStricker, Bruno, H1 aPsaty, Bruce, M1 aCiullo, Marina1 aSanna, Serena1 aLehtimäki, Terho1 aWilson, James, F1 aBandinelli, Stefania1 aAlonso, Alvaro1 aGasparini, Paolo1 aJukema, Wouter1 aKääb, Stefan1 aGudnason, Vilmundur1 aFelix, Stephan, B1 aHeckbert, Susan, R1 ade Boer, Rudolf, A1 aNewton-Cheh, Christopher1 aHicks, Andrew, A1 aChambers, John, C1 aJamshidi, Yalda1 aVisel, Axel1 aChristoffels, Vincent, M1 aIsaacs, Aaron1 aSamani, Nilesh, J1 ade Bakker, Paul, I W uhttps://chs-nhlbi.org/node/726203786nas a2200841 4500008004100000022001400041245009800055210006900153260001300222300001300235490000700248520140700255100001801662700002101680700002401701700002801725700002001753700001901773700001801792700001801810700002001828700002301848700001901871700002001890700001801910700001901928700001801947700002201965700001701987700002502004700002002029700001902049700002102068700002102089700002302110700002402133700002002157700001402177700001402191700001602205700002202221700001502243700002602258700002802284700001702312700002102329700001902350700002602369700002802395700002002423700002402443700002602467700001902493700001702512700001702529700002002546700002502566700001902591700001802610700002102628700002102649700002102670700002902691700001802720700002702738700002302765700002302788710002602811710002302837710002202860710002602882856003602908 2016 eng d a1553-740400aDiscovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure.0 aDiscovery of Genetic Variation on Chromosome 5q22 Associated wit c2016 May ae10060340 v123 aFailure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure.
1 aSmith, Gustav1 aFelix, Janine, F1 aMorrison, Alanna, C1 aKalogeropoulos, Andreas1 aTrompet, Stella1 aWilk, Jemma, B1 aGidlöf, Olof1 aWang, Xinchen1 aMorley, Michael1 aMendelson, Michael1 aJoehanes, Roby1 aLigthart, Symen1 aShan, Xiaoyin1 aBis, Joshua, C1 aWang, Ying, A1 aSjögren, Marketa1 aNgwa, Julius1 aBrandimarto, Jeffrey1 aStott, David, J1 aAguilar, David1 aRice, Kenneth, M1 aSesso, Howard, D1 aDemissie, Serkalem1 aBuckley, Brendan, M1 aTaylor, Kent, D1 aFord, Ian1 aYao, Chen1 aLiu, Chunyu1 aSotoodehnia, Nona1 aHarst, Pim1 aStricker, Bruno, H Ch1 aKritchevsky, Stephen, B1 aLiu, Yongmei1 aGaziano, Michael1 aHofman, Albert1 aMoravec, Christine, S1 aUitterlinden, André, G1 aKellis, Manolis1 avan Meurs, Joyce, B1 aMargulies, Kenneth, B1 aDehghan, Abbas1 aLevy, Daniel1 aOlde, Björn1 aPsaty, Bruce, M1 aCupples, Adrienne, L1 aJukema, Wouter1 aDjoussé, Luc1 aFranco, Oscar, H1 aBoerwinkle, Eric1 aBoyer, Laurie, A1 aNewton-Cheh, Christopher1 aButler, Javed1 aVasan, Ramachandran, S1 aCappola, Thomas, P1 aSmith, Nicholas, L1 aCHARGE-SCD consortium1 aEchoGen consortium1 aQT-IGC consortium1 aCHARGE-QRS consortium uhttps://chs-nhlbi.org/node/714403045nas a2200709 4500008004100000022001400041245009300055210006900148260001500217300001400232490000700246520089300253653004101146653002501187653004901212653002101261653003801282653002701320653002401347653001101371653003801382653003401420653002801454653001101482653000901493653004001502653003601542653002301578653002801601653002801629100001801657700002401675700001801699700001901717700001901736700001801755700002801773700002801801700001801829700001801847700002401865700002301889700002001912700002801932700001701960700002301977700002202000700002202022700002102044700002402065700002102089700001902110700001902129700002202148700002202170700002302192700002502215700001702240700001502257710002702272856003602299 2016 eng d a1460-208300aTwenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram.0 aTwentyeight genetic loci associated with STTwave amplitudes of t c2016 05 15 a2093-21030 v253 aThe ST-segment and adjacent T-wave (ST-T wave) amplitudes of the electrocardiogram are quantitative characteristics of cardiac repolarization. Repolarization abnormalities have been linked to ventricular arrhythmias and sudden cardiac death. We performed the first genome-wide association meta-analysis of ST-T-wave amplitudes in up to 37 977 individuals identifying 71 robust genotype-phenotype associations clustered within 28 independent loci. Fifty-four genes were prioritized as candidates underlying the phenotypes, including genes with established roles in the cardiac repolarization phase (SCN5A/SCN10A, KCND3, KCNB1, NOS1AP and HEY2) and others with as yet undefined cardiac function. These associations may provide insights in the spatiotemporal contribution of genetic variation influencing cardiac repolarization and provide novel leads for future functional follow-up.
10aAdaptor Proteins, Signal Transducing10aArrhythmias, Cardiac10aBasic Helix-Loop-Helix Transcription Factors10aBrugada Syndrome10aCardiac Conduction System Disease10aDeath, Sudden, Cardiac10aElectrocardiography10aFemale10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHeart Conduction System10aHumans10aMale10aNAV1.5 Voltage-Gated Sodium Channel10aPolymorphism, Single Nucleotide10aRepressor Proteins10aShab Potassium Channels10aShal Potassium Channels1 aVerweij, Niek1 aLeach, Irene, Mateo1 aIsaacs, Aaron1 aArking, Dan, E1 aBis, Joshua, C1 aPers, Tune, H1 avan den Berg, Marten, E1 aLyytikäinen, Leo-Pekka1 aBarnett, Phil1 aWang, Xinchen1 aSoliman, Elsayed, Z1 aDuijn, Cornelia, M1 aKähönen, Mika1 avan Veldhuisen, Dirk, J1 aKors, Jan, A1 aRaitakari, Olli, T1 aSilva, Claudia, T1 aLehtimäki, Terho1 aHillege, Hans, L1 aHirschhorn, Joel, N1 aBoyer, Laurie, A1 aGilst, Wiek, H1 aAlonso, Alvaro1 aSotoodehnia, Nona1 aEijgelsheim, Mark1 ade Boer, Rudolf, A1 ade Bakker, Paul, I W1 aFranke, Lude1 aHarst, Pim1 aLifeLines Cohort Study uhttps://chs-nhlbi.org/node/7604