PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Almenn færsla
dc.contributorHáskóli Íslands (HÍ)en_US
dc.contributorUniversity of Iceland (UI)en_US
dc.contributor.authorvan Setten, Jessica
dc.contributor.authorBrody, Jennifer A.
dc.contributor.authorJamshidi, Yalda
dc.contributor.authorSwenson, Brenton R.
dc.contributor.authorButler, Anne M.
dc.contributor.authorCampbell, Harry
dc.contributor.authorDel Greco, Fabiola M.
dc.contributor.authorEvans, Daniel S.
dc.contributor.authorGibson, Quince
dc.contributor.authorGudbjartsson, Daniel
dc.contributor.authorKerr, Kathleen F.
dc.contributor.authorKrijthe, Bouwe P.
dc.contributor.authorLyytikäinen, Leo-Pekka
dc.contributor.authorMüller, Christian
dc.contributor.authorMüller-Nurasyid, Martina
dc.contributor.authorNolte, Ilja M.
dc.contributor.authorPadmanabhan, Sandosh
dc.contributor.authorRitchie, Marylyn D.
dc.contributor.authorRobino, Antonietta
dc.contributor.authorSmith, Albert Vernon
dc.contributor.authorSteri, Maristella
dc.contributor.authorTanaka, Toshiko
dc.contributor.authorTeumer, Alexander
dc.contributor.authorTrompet, Stella
dc.contributor.authorUlivi, Sheila
dc.contributor.authorVerweij, Niek
dc.contributor.authorYin, Xiaoyan
dc.contributor.authorArnar, Davíð O.
dc.contributor.authorAsselbergs, Folkert W.
dc.contributor.authorBader, Joel S.
dc.contributor.authorBarnard, John
dc.contributor.authorBis, Josh
dc.contributor.authorBlankenberg, Stefan
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorBradford, Yuki
dc.contributor.authorBuckley, Brendan M.
dc.contributor.authorChung, Mina K.
dc.contributor.authorCrawford, Dana
dc.contributor.authorden Hoed, Marcel
dc.contributor.authorDenny, Josh C.
dc.contributor.authorDominiczak, Anna F.
dc.contributor.authorEhret, Georg B.
dc.contributor.authorEijgelsheim, Mark
dc.contributor.authorEllinor, Patrick T.
dc.contributor.authorFelix, Stephan B.
dc.contributor.authorFranco, Oscar H.
dc.contributor.authorFranke, Lude
dc.contributor.authorHarris, Tamara B.
dc.contributor.authorHolm, Hilma
dc.contributor.authorIlaria, Gandin
dc.contributor.authorIorio, Annamaria
dc.contributor.authorKähönen, Mika
dc.contributor.authorKolcic, Ivana
dc.contributor.authorKors, Jan A.
dc.contributor.authorLakatta, Edward G.
dc.contributor.authorLauner, Lenore J.
dc.contributor.authorLin, Honghuang
dc.contributor.authorLin, Henry J.
dc.contributor.authorLoos, Ruth J. F.
dc.contributor.authorLubitz, Steven A.
dc.contributor.authorMacfarlane, Peter W.
dc.contributor.authorMagnani, Jared W.
dc.contributor.authorLeach, Irene Mateo
dc.contributor.authorMeitinger, Thomas
dc.contributor.authorMitchell, Braxton D.
dc.contributor.authorMunzel, Thomas
dc.contributor.authorPapanicolaou, George J.
dc.contributor.authorPeters, Annette
dc.contributor.authorPfeufer, Arne
dc.contributor.authorPramstaller, Peter P.
dc.contributor.authorRaitakari, Olli T.
dc.contributor.authorRotter, Jerome I.
dc.contributor.authorRudan, Igor
dc.contributor.authorSamani, Nilesh J.
dc.contributor.authorSchlessinger, David
dc.contributor.authorSilva Aldana, Claudia T.
dc.contributor.authorSinner, Moritz F.
dc.contributor.authorSmith, Jonathan D.
dc.contributor.authorSnieder, Harold
dc.contributor.authorSoliman, Elsayed Z.
dc.contributor.authorSpector, Timothy D.
dc.contributor.authorStott, David J.
dc.contributor.authorStrauch, Konstantin
dc.contributor.authorTarasov, Kirill V.
dc.contributor.authorÞorsteinsdóttir, Unnur
dc.contributor.authorUitterlinden, Andre G.
dc.contributor.authorVan Wagoner, David R.
dc.contributor.authorVölker, Uwe
dc.contributor.authorVölzke, Henry
dc.contributor.authorWaldenberger, Melanie
dc.contributor.authorJan Westra, Harm
dc.contributor.authorWild, Philipp S.
dc.contributor.authorZeller, Tanja
dc.contributor.authorAlonso, Alvaro
dc.contributor.authorAvery, Christy L.
dc.contributor.authorBandinelli, Stefania
dc.contributor.authorBenjamin, Emelia J.
dc.contributor.authorCucca, Francesco
dc.contributor.authorDörr, Marcus
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorGasparini, Paolo
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorHayward, Caroline
dc.contributor.authorHeckbert, Susan R.
dc.contributor.authorHicks, Andrew A.
dc.contributor.authorJukema, J. Wouter
dc.contributor.authorKääb, Stefan
dc.contributor.authorLehtimäki, Terho
dc.contributor.authorLiu, Yongmei
dc.contributor.authorMunroe, Patricia B.
dc.contributor.authorParsa, Afshin
dc.contributor.authorPolasek, Ozren
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorRoden, Dan M.
dc.contributor.authorSchnabel, Renate B.
dc.contributor.authorSinagra, Gianfranco
dc.contributor.authorStefansson, Kari
dc.contributor.authorStricker, Bruno H.
dc.contributor.authorvan der Harst, Pim
dc.contributor.authorvan Duijn, Cornelia M.
dc.contributor.authorWilson, James F.
dc.contributor.authorGharib, Sina A.
dc.contributor.authorde Bakker, Paul I. W.
dc.contributor.authorIsaacs, Aaron
dc.contributor.authorArking, Dan E.
dc.contributor.authorSotoodehnia, Nona
dc.contributor.departmentFaculty of Medicine (UI)en_US
dc.contributor.departmentLæknadeild (HÍ)en_US
dc.contributor.schoolSchool of Engineering and Natural Sciences (UI)en_US
dc.contributor.schoolVerkfræði- og náttúruvísindasvið (HÍ)en_US
dc.contributor.schoolSchool of Health Sciences (UI)en_US
dc.contributor.schoolHeilbrigðisvísindasvið (HÍ)en_US
dc.date.accessioned2019-12-16T11:33:23Z
dc.date.available2019-12-16T11:33:23Z
dc.date.issued2018-07-25
dc.descriptionPublisher's version (útgefin grein). Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.en_US
dc.description.abstractElectrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.en_US
dc.description.sponsorshipAcknowledgements per cohort are listed in Supplementary Note 2. We thank the following studies for sharing their summary level results: QRS voltage (van der Harst et al., 2016)[12], heart rate (den Hoed et al., 2013)[35], RR interval (Eijgelsheim et al., 2010)[11], atrial fibrillation (Christophersen et al., 2017[15]), and CARe-COGENT AA PR Consortium (Butler et al., 2012)[33]. We acknowledge Dr. Vinicius Tragante for his help generating the author list.en_US
dc.description.versionPeer Revieweden_US
dc.format.extent2904en_US
dc.identifier.citationvan Setten, J., Brody, J.A., Jamshidi, Y. et al. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity. Nat Commun 9, 2904 (2018) doi:10.1038/s41467-018-04766-9en_US
dc.identifier.doi10.1038/s41467-018-04766-9
dc.identifier.issn2041-1723
dc.identifier.journalNature Communicationsen_US
dc.identifier.urihttps://hdl.handle.net/20.500.11815/1392
dc.language.isoenen_US
dc.publisherSpringer Science and Business Media LLCen_US
dc.relation.ispartofseriesNature Communications;9(1)
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAtrial Fibrillationen_US
dc.subjectHeart Diseasesen_US
dc.subjectHeart Blocken_US
dc.subjectGenome-Wide Association Studyen_US
dc.subjectCardiovascular geneticsen_US
dc.titlePR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activityen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dcterms.licenseOpen Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en_US

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