Publication:
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

cris.virtualsource.author-orcid16b220c7-d094-4a4a-a8bf-82a2b1cdbed5
datacite.rightsrestricted
dc.contributor.authorArking, Dan E
dc.contributor.authorPulit, Sara L
dc.contributor.authorCrotti, Lia
dc.contributor.authorvan der Harst, Pim
dc.contributor.authorMunroe, Patricia B
dc.contributor.authorKoopmann, Tamara T
dc.contributor.authorSotoodehnia, Nona
dc.contributor.authorRossin, Elizabeth J
dc.contributor.authorMorley, Michael
dc.contributor.authorWang, Xinchen
dc.contributor.authorJohnson, Andrew D
dc.contributor.authorLundby, Alicia
dc.contributor.authorGudbjartsson, Daníel F
dc.contributor.authorNoseworthy, Peter A
dc.contributor.authorEijgelsheim, Mark
dc.contributor.authorBradford, Yuki
dc.contributor.authorTarasov, Kirill V
dc.contributor.authorDörr, Marcus
dc.contributor.authorMüller-Nurasyid, Martina
dc.contributor.authorLahtinen, Annukka M
dc.contributor.authorNolte, Ilja M
dc.contributor.authorSmith, Albert Vernon
dc.contributor.authorBis, Joshua C
dc.contributor.authorIsaacs, Aaron
dc.contributor.authorNewhouse, Stephen J
dc.contributor.authorEvans, Daniel S
dc.contributor.authorPost, Wendy S
dc.contributor.authorWaggott, Daryl
dc.contributor.authorLyytikäinen, Leo-Pekka
dc.contributor.authorHicks, Andrew A
dc.contributor.authorEisele, Lewin
dc.contributor.authorEllinghaus, David
dc.contributor.authorHayward, Caroline
dc.contributor.authorNavarro, Pau
dc.contributor.authorUlivi, Sheila
dc.contributor.authorTanaka, Toshiko
dc.contributor.authorTester, David J
dc.contributor.authorChatel, Stéphanie
dc.contributor.authorGustafsson, Stefan
dc.contributor.authorKumari, Meena
dc.contributor.authorMorris, Richard W
dc.contributor.authorNaluai, Åsa T
dc.contributor.authorPadmanabhan, Sandosh
dc.contributor.authorKluttig, Alexander
dc.contributor.authorStrohmer, Bernhard
dc.contributor.authorPanayiotou, Andrie G
dc.contributor.authorTorres, Maria
dc.contributor.authorKnoflach, Michael
dc.contributor.authorHubacek, Jaroslav A
dc.contributor.authorSlowikowski, Kamil
dc.contributor.authorRaychaudhuri, Soumya
dc.contributor.authorKumar, Runjun D
dc.contributor.authorHarris, Tamara B
dc.contributor.authorLauner, Lenore J
dc.contributor.authorShuldiner, Alan R
dc.contributor.authorAlonso, Alvaro
dc.contributor.authorBader, Joel S
dc.contributor.authorEhret, Georg
dc.contributor.authorHuang, Hailiang
dc.contributor.authorKao, W H Linda
dc.contributor.authorStrait, James B
dc.contributor.authorMacfarlane, Peter W
dc.contributor.authorBrown, Morris
dc.contributor.authorCaulfield, Mark J
dc.contributor.authorSamani, Nilesh J
dc.contributor.authorKronenberg, Florian
dc.contributor.authorWilleit, Johann
dc.contributor.authorGreiser, Karin H
dc.contributor.authorMeyer Zu Schwabedissen, Henriette
dc.contributor.authorWerdan, Karl
dc.contributor.authorCarella, Massimo
dc.contributor.authorZelante, Leopoldo
dc.contributor.authorHeckbert, Susan R
dc.contributor.authorPsaty, Bruce M
dc.contributor.authorRotter, Jerome I
dc.contributor.authorKolcic, Ivana
dc.contributor.authorPolašek, Ozren
dc.contributor.authorWright, Alan F
dc.contributor.authorGriffin, Maura
dc.contributor.authorDaly, Mark J
dc.contributor.authorArnar, David O
dc.contributor.authorHólm, Hilma
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorDenny, Joshua C
dc.contributor.authorRoden, Dan M
dc.contributor.authorZuvich, Rebecca L
dc.contributor.authorEmilsson, Valur
dc.contributor.authorPlump, Andrew S
dc.contributor.authorLarson, Martin G
dc.contributor.authorO'Donnell, Christopher J
dc.contributor.authorYin, Xiaoyan
dc.contributor.authorBobbo, Marco
dc.contributor.authorD'Adamo, Adamo P
dc.contributor.authorIorio, Annamaria
dc.contributor.authorSinagra, Gianfranco
dc.contributor.authorCarracedo, Angel
dc.contributor.authorCummings, Steven R
dc.contributor.authorNalls, Michael A
dc.contributor.authorJula, Antti
dc.contributor.authorKontula, Kimmo K
dc.contributor.authorMarjamaa, Annukka
dc.contributor.authorOikarinen, Lasse
dc.contributor.authorPerola, Markus
dc.contributor.authorPorthan, Kimmo
dc.contributor.authorErbel, Raimund
dc.contributor.authorHoffmann, Per
dc.contributor.authorJöckel, Karl-Heinz
dc.contributor.authorKälsch, Hagen
dc.contributor.authorNöthen, Markus M
dc.contributor.authorden Hoed, Marcel
dc.contributor.authorLoos, Ruth J F
dc.contributor.authorThelle, Dag S
dc.contributor.authorGieger, Christian
dc.contributor.authorMeitinger, Thomas
dc.contributor.authorPerz, Siegfried
dc.contributor.authorPeters, Annette
dc.contributor.authorPrucha, Hanna
dc.contributor.authorSinner, Moritz F
dc.contributor.authorWaldenberger, Melanie
dc.contributor.authorde Boer, Rudolf A
dc.contributor.authorFranke, Lude
dc.contributor.authorvan der Vleuten, Pieter A
dc.contributor.authorBeckmann, Britt Maria
dc.contributor.authorMartens, Eimo
dc.contributor.authorBardai, Abdennasser
dc.contributor.authorHofman, Nynke
dc.contributor.authorWilde, Arthur A M
dc.contributor.authorBehr, Elijah R
dc.contributor.authorDalageorgou, Chrysoula
dc.contributor.authorGiudicessi, John R
dc.contributor.authorMedeiros Domingo, Argelia
dc.contributor.authorBarc, Julien
dc.contributor.authorKyndt, Florence
dc.contributor.authorProbst, Vincent
dc.contributor.authorGhidoni, Alice
dc.contributor.authorInsolia, Roberto
dc.contributor.authorHamilton, Robert M
dc.contributor.authorScherer, Stephen W
dc.contributor.authorBrandimarto, Jeffrey
dc.contributor.authorMargulies, Kenneth
dc.contributor.authorMoravec, Christine E
dc.contributor.authordel Greco M, Fabiola
dc.contributor.authorFuchsberger, Christian
dc.contributor.authorO'Connell, Jeffrey R
dc.contributor.authorLee, Wai K
dc.contributor.authorWatt, Graham C M
dc.contributor.authorCampbell, Harry
dc.contributor.authorWild, Sarah H
dc.contributor.authorEl Mokhtari, Nour E
dc.contributor.authorFrey, Norbert
dc.contributor.authorAsselbergs, Folkert W
dc.contributor.authorMateo Leach, Irene
dc.contributor.authorNavis, Gerjan
dc.contributor.authorvan den Berg, Maarten P
dc.contributor.authorvan Veldhuisen, Dirk J
dc.contributor.authorKellis, Manolis
dc.contributor.authorKrijthe, Bouwe P
dc.contributor.authorFranco, Oscar H
dc.contributor.authorHofman, Albert
dc.contributor.authorKors, Jan A
dc.contributor.authorUitterlinden, André G
dc.contributor.authorWitteman, Jacqueline C M
dc.contributor.authorKedenko, Lyudmyla
dc.contributor.authorLamina, Claudia
dc.contributor.authorOostra, Ben A
dc.contributor.authorAbecasis, Gonçalo R
dc.contributor.authorLakatta, Edward G
dc.contributor.authorMulas, Antonella
dc.contributor.authorOrrú, Marco
dc.contributor.authorSchlessinger, David
dc.contributor.authorUda, Manuela
dc.contributor.authorMarkus, Marcello R P
dc.contributor.authorVölker, Uwe
dc.contributor.authorSnieder, Harold
dc.contributor.authorSpector, Timothy D
dc.contributor.authorÄrnlöv, Johan
dc.contributor.authorLind, Lars
dc.contributor.authorSundström, Johan
dc.contributor.authorSyvänen, Ann-Christine
dc.contributor.authorKivimaki, Mika
dc.contributor.authorKähönen, Mika
dc.contributor.authorMononen, Nina
dc.contributor.authorRaitakari, Olli T
dc.contributor.authorViikari, Jorma S
dc.contributor.authorAdamkova, Vera
dc.contributor.authorKiechl, Stefan
dc.contributor.authorBrion, Maria
dc.contributor.authorNicolaides, Andrew N
dc.contributor.authorPaulweber, Bernhard
dc.contributor.authorHaerting, Johannes
dc.contributor.authorDominiczak, Anna F
dc.contributor.authorNyberg, Fredrik
dc.contributor.authorWhincup, Peter H
dc.contributor.authorHingorani, Aroon D
dc.contributor.authorSchott, Jean-Jacques
dc.contributor.authorBezzina, Connie R
dc.contributor.authorIngelsson, Erik
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorGasparini, Paolo
dc.contributor.authorWilson, James F
dc.contributor.authorRudan, Igor
dc.contributor.authorFranke, Andre
dc.contributor.authorMühleisen, Thomas W
dc.contributor.authorPramstaller, Peter P
dc.contributor.authorLehtimäki, Terho J
dc.contributor.authorPaterson, Andrew D
dc.contributor.authorParsa, Afshin
dc.contributor.authorLiu, Yongmei
dc.contributor.authorvan Duijn, Cornelia M
dc.contributor.authorSiscovick, David S
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorJamshidi, Yalda
dc.contributor.authorSalomaa, Veikko
dc.contributor.authorFelix, Stephan B
dc.contributor.authorSanna, Serena
dc.contributor.authorRitchie, Marylyn D
dc.contributor.authorStricker, Bruno H
dc.contributor.authorStefansson, Kari
dc.contributor.authorBoyer, Laurie A
dc.contributor.authorCappola, Thomas P
dc.contributor.authorOlsen, Jesper V
dc.contributor.authorLage, Kasper
dc.contributor.authorSchwartz, Peter J
dc.contributor.authorKääb, Stefan
dc.contributor.authorChakravarti, Aravinda
dc.contributor.authorAckerman, Michael J
dc.contributor.authorPfeufer, Arne
dc.contributor.authorde Bakker, Paul I W
dc.contributor.authorNewton-Cheh, Christopher
dc.date.accessioned2024-10-23T17:38:29Z
dc.date.available2024-10-23T17:38:29Z
dc.date.issued2014-08
dc.description.abstractThe 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.
dc.description.numberOfPages11
dc.description.sponsorshipUniversitätsklinik für Kardiologie
dc.identifier.doi10.7892/boris.63883
dc.identifier.pmid24952745
dc.identifier.publisherDOI10.1038/ng.3014
dc.identifier.urihttps://boris-portal.unibe.ch/handle/20.500.12422/129758
dc.language.isoen
dc.publisherNature America
dc.relation.ispartofNature genetics
dc.relation.issn1061-4036
dc.relation.organizationDCD5A442BB15E17DE0405C82790C4DE2
dc.subject.ddc600 - Technology::610 - Medicine & health
dc.subject.ddc500 - Science::570 - Life sciences; biology
dc.titleGenetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
dc.typearticle
dspace.entity.typePublication
dspace.file.typetext
oaire.citation.endPage836
oaire.citation.issue8
oaire.citation.startPage826
oaire.citation.volume46
oairecerif.author.affiliationUniversitätsklinik für Kardiologie
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