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

Electrocardiographic 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). Exami...

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Fecha de publicación:: 2018

Institución:: Universidad del Rosario

Repositorio:: Repositorio EdocUR - U. Rosario

Idioma:: eng

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repository_id_str
dc.title.spa.fl_str_mv	PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
title	PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
spellingShingle	PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity Gudnason, Vilmundur Ion Channel Transcription Factor Disequilibrium Genetic Analysis Genome Meta-Analysis Risk Factor African Atrial Fibrillation Atrioventricular Conduction Cell Junction Electric Activity European Gene Linkage Disequilibrium Gene Locus Genome-Wide Association Study Heart Block Heart Depolarization Heart Rate Human Missense Mutation Phenotype Pr Interval Qrs Interval Signal Transduction Canal de iones Factor de transcripción Sangre Sistema cardiovascular Enfermedades Cardiovascular system Blood Heart Disease Article Enfermedades cardiovasculares Fibrilación auricular Bloqueo cardíaco
title_short	PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
title_full	PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
title_fullStr	PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
title_full_unstemmed	PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
title_sort	PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
dc.creator.none.fl_str_mv	Gudnason, Vilmundur Hayward, Caroline Heckbert, Susan R. Hicks, Andrew A. Jukema, J. Wouter Kääb, Stefan Lehtimäk, Terho Liu, Yongmei Munroe, Patricia B. Parsa, Afshin Polasek, Ozren Psaty, Bruce M. Roden, Dan M. Schnabel, Renate B. Sinagra, Gianfranco Stefansson, Kari Stricker, Bruno H. Harst, Pim van der Duijn, Cornelia M. van Wilson, James F. Gharib, Sina A. Bakker, Paul I.W. de Isaacs, Aaron Arking, Dan E. Sotoodehnia, Nona
dc.creator.google.spa.fl_str_mv	van Setten, Jessica Brody, Jennifer A. Jamshidi, Yalda Swenson, Brenton R. Butler, Anne M. Campbell, Harry Del Greco, Fabiola M. Evans, Daniel S. Gibson, Quince Gudbjartsson, Daniel F. Kerr, Kathleen F. Krijthe, Bouwe P. Lyytikäinen, Leo-Pekka Müller, Christian Müller-Nurasyid, Martina Nolte, Ilja M. Padmanabhan, Sandosh Ritchie, Marylyn D. Robino, Antonietta Smith, Albert V. Steri, Maristella Tanaka, Toshiko Teumer, Alexander Trompet, Stella Ulivi, Sheila Verweij, Niek Yin, Xiaoyan Arnar, David O. Asselbergs, Folkert W. Bader, Joel S. Barnard, John Bis, Josh Blankenberg, Stefan Boerwinkle, Eric Bradford, Yuki Buckley, Brendan M. Chung, Mina K. Crawford, Dana den Hoed, Marcel Denny, Josh C. Dominiczak, Anna F. Ehret, Georg B. Eijgelsheim, Mark Ellinor, Patrick T. Felix, Stephan B. Franco, Oscar H. Franke, Lude Harris, Tamara B. Holm, Hilma Ilaria, Gandin Iorio, Annamaria Kähönen, Mika Kolcic, Ivana Kors, Jan A. Lakatta, Edward G. Launer, Lenore J. Lin, Honghuang Lin, Henry J. Loos, Ruth J.F. Lubitz, Steven A. Macfarlane, Peter W. Magnani, Jared W. Mateo Leach, Irene Meitinger, Thomas Mitchell, Braxton D. Munzel, Thomas Papanicolaou, George J. Peters, Annette Pfeufer, Arne Pramstaller, Peter P. Raitakari, Olli T. Rotter, Jerome I. Rudan, Igor Samani, Nilesh J. Schlessinger, David Silva Aldana, Claudia T. Sinner, Moritz F. Smith, Jonathan D. Snieder, Harold Soliman, Elsayed Z. Spector, Timothy D. Stott, David J. Strauch, Konstantin Tarasov, Kirill V. Thorsteinsdottir, Unnur Uitterlinden, Andre G. Van Wagoner, David R. Völker, Uwe Völzke, Henry Waldenberger, Melanie Jan Westra, Harm Wild, Philipp S. Zeller, Tanja Alonso, Alvaro Avery, Christy L. Bandinelli, Stefania Benjamin, Emelia J. Cucca, Francesco Dörr, Marcus Ferrucci, Luigi Gasparini, Paolo Gudnason, Vilmundur Hayward, Caroline Heckbert, Susan R. Hicks, Andrew A. Jukema, J. Wouter Kääb, Stefan Lehtimäki, Terho Liu, Yongmei Munroe, Patricia B. Parsa, Afshin Polasek, Ozren Psaty, Bruce M. Roden, Dan M. Schnabel, Renate B. Sinagra, Gianfranco Stefansson, Kari Stricker, Bruno H. van der Harst, Pim van Duijn, Cornelia M. Wilson,James F. Gharib, Sina A. de Bakker, Paul I.W. Isaacs, Aaron Arking, Dan E. Sotoodehnia, Nona
author	Gudnason, Vilmundur
author_facet	Gudnason, Vilmundur Hayward, Caroline Heckbert, Susan R. Hicks, Andrew A. Jukema, J. Wouter Kääb, Stefan Lehtimäk, Terho Liu, Yongmei Munroe, Patricia B. Parsa, Afshin Polasek, Ozren Psaty, Bruce M. Roden, Dan M. Schnabel, Renate B. Sinagra, Gianfranco Stefansson, Kari Stricker, Bruno H. Harst, Pim van der Duijn, Cornelia M. van Wilson, James F. Gharib, Sina A. Bakker, Paul I.W. de Isaacs, Aaron Arking, Dan E. Sotoodehnia, Nona
author_role	author
author2	Hayward, Caroline Heckbert, Susan R. Hicks, Andrew A. Jukema, J. Wouter Kääb, Stefan Lehtimäk, Terho Liu, Yongmei Munroe, Patricia B. Parsa, Afshin Polasek, Ozren Psaty, Bruce M. Roden, Dan M. Schnabel, Renate B. Sinagra, Gianfranco Stefansson, Kari Stricker, Bruno H. Harst, Pim van der Duijn, Cornelia M. van Wilson, James F. Gharib, Sina A. Bakker, Paul I.W. de Isaacs, Aaron Arking, Dan E. Sotoodehnia, Nona
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.spa.fl_str_mv	Ion Channel Transcription Factor Disequilibrium Genetic Analysis Genome Meta-Analysis Risk Factor African Atrial Fibrillation Atrioventricular Conduction Cell Junction Electric Activity European Gene Linkage Disequilibrium Gene Locus Genome-Wide Association Study Heart Block Heart Depolarization Heart Rate Human Missense Mutation Phenotype Pr Interval Qrs Interval Signal Transduction Canal de iones Factor de transcripción Sangre Sistema cardiovascular
topic	Ion Channel Transcription Factor Disequilibrium Genetic Analysis Genome Meta-Analysis Risk Factor African Atrial Fibrillation Atrioventricular Conduction Cell Junction Electric Activity European Gene Linkage Disequilibrium Gene Locus Genome-Wide Association Study Heart Block Heart Depolarization Heart Rate Human Missense Mutation Phenotype Pr Interval Qrs Interval Signal Transduction Canal de iones Factor de transcripción Sangre Sistema cardiovascular Enfermedades Cardiovascular system Blood Heart Disease Article Enfermedades cardiovasculares Fibrilación auricular Bloqueo cardíaco
dc.subject.ddc.spa.fl_str_mv	Enfermedades
dc.subject.keyword.spa.fl_str_mv	Cardiovascular system Blood Heart Disease Article
dc.subject.lemb.spa.fl_str_mv	Enfermedades cardiovasculares Fibrilación auricular Bloqueo cardíaco
description	Electrocardiographic 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. © 2018, The Author(s).
publishDate	2018
dc.date.created.none.fl_str_mv	2018
dc.date.issued.none.fl_str_mv	2018
dc.date.accessioned.none.fl_str_mv	2019-10-17T12:55:20Z
dc.date.available.none.fl_str_mv	2019-10-17T12:55:20Z
dc.type.eng.fl_str_mv	article
dc.type.coarversion.fl_str_mv	http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.coar.fl_str_mv	http://purl.org/coar/resource_type/c_6501
dc.type.spa.spa.fl_str_mv	Artículo
dc.identifier.doi.none.fl_str_mv	10.1038/s41467-018-04766-9
dc.identifier.issn.none.fl_str_mv	2041-1723
dc.identifier.uri.none.fl_str_mv	https://repository.urosario.edu.co/handle/10336/20449
identifier_str_mv	10.1038/s41467-018-04766-9 2041-1723
url	https://repository.urosario.edu.co/handle/10336/20449
dc.language.iso.spa.fl_str_mv	eng
language	eng
dc.relation.citationTitle.none.fl_str_mv	Nature Communications
dc.relation.citationVolume.none.fl_str_mv	Vol. 9
dc.relation.ispartof.spa.fl_str_mv	Nature Communications, ISSN:2041-1723, Vol. 9 (2018)
dc.relation.uri.spa.fl_str_mv	https://www.nature.com/articles/s41467-018-04766-9
dc.rights.coar.fl_str_mv	http://purl.org/coar/access_right/c_abf2
dc.rights.acceso.spa.fl_str_mv	Abierto (Texto Completo)
rights_invalid_str_mv	Abierto (Texto Completo) http://purl.org/coar/access_right/c_abf2
dc.format.mimetype.none.fl_str_mv	application/pdf
institution	Universidad del Rosario
dc.source.bibliographicCitation.spa.fl_str_mv	Kannel, W.B., Benjamin, E.J., Current perceptions of the epidemiology of atrial fibrillation (2009) Cardiol. Clin., 27, pp. 13-24. , PID: 19111760
dc.source.instname.none.fl_str_mv	instname:Universidad del Rosario
dc.source.reponame.none.fl_str_mv	reponame:Repositorio Institucional EdocUR
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WouterKääb, StefanLehtimäki, TerhoLiu, YongmeiMunroe, Patricia B.Parsa, AfshinPolasek, OzrenPsaty, Bruce M.Roden, Dan M.Schnabel, Renate B.Sinagra, GianfrancoStefansson, KariStricker, Bruno H.van der Harst, Pimvan Duijn, Cornelia M.Wilson,James F.Gharib, Sina A.de Bakker, Paul I.W.Isaacs, AaronArking, Dan E.Sotoodehnia, Nona2019-10-17T12:55:20Z2019-10-17T12:55:20Z20182018Electrocardiographic 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. © 2018, The Author(s).application/pdf10.1038/s41467-018-04766-92041-1723https://repository.urosario.edu.co/handle/10336/20449engNature CommunicationsVol. 9Nature Communications, ISSN:2041-1723, Vol. 9 (2018)https://www.nature.com/articles/s41467-018-04766-9Abierto (Texto Completo)http://purl.org/coar/access_right/c_abf2Kannel, W.B., Benjamin, E.J., Current perceptions of the epidemiology of atrial fibrillation (2009) Cardiol. Clin., 27, pp. 13-24. , PID: 19111760instname:Universidad del Rosarioreponame:Repositorio Institucional EdocURIon ChannelTranscription FactorDisequilibriumGenetic AnalysisGenomeMeta-AnalysisRisk FactorAfricanAtrial FibrillationAtrioventricular ConductionCell JunctionElectric ActivityEuropeanGene Linkage DisequilibriumGene LocusGenome-Wide Association StudyHeart BlockHeart DepolarizationHeart RateHumanMissense MutationPhenotypePr IntervalQrs IntervalSignal TransductionCanal de ionesFactor de transcripciónSangreSistema cardiovascularEnfermedades616600Cardiovascular systemBloodHeart DiseaseArticleEnfermedades cardiovascularesFibrilación auricularBloqueo cardíacoPR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activityarticleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501van Setten, JessicaBrody, Jennifer A.Jamshidi, YaldaSwenson, Brenton R.Butler, Anne M.Campbell, HarryDel Greco, Fabiola M.Evans, Daniel S.Gibson, QuinceGudbjartsson, Daniel F.Kerr, KathleenKrijthe, Bouwe P.Lyytikäinen, Leo-PekkaMüller, ChristianMüller-Nurasyid, MartinaNolte, Ilja M.Padmanabhan, SandoshRitchie, Marylyn D.Robino, AntoniettaSmith, Albert V.Steri, MaristellaTanaka, ToshikoTeumer, AlexanderTrompet, StellaUlivi, SheilaVerweij, NiekYin, XiaoyanArnar, David O.Asselbergs, Folkert W.Bader, Joel S.Barnard, JohnBis, JoshBlankenberg, StefanBoerwinkle, EricBradford, YukiBuckley, Brendan M.Chung, Mina K.Crawford, Danaden Hoed, MarcelDenny, Josh C.Dominiczak, Anna F.Ehret, Georg B.Eijgelsheim, MarkEllinor, Patrick T.Felix, Stephan B.Franco, Oscar H.Franke, LudeHarris, Tamara B.Holm, HilmaGANDIN, ILARIAIorio, AnnamariaKähönen, MikaKolcic, IvanaKors, Jan A.Lakatta, Edward G.Launer, Lenore J.Lin, HonghuangLin, Henry J.Loos, Ruth J.F.Lubitz, Steven A.Macfarlane, Peter W.Magnani, Jared W.Mateo Leach, IreneMeitinger, ThomasMitchell, Braxton D.Munzel, ThomasPapanicolaou, George J.Peters, AnnettePfeufer, ArnePramstaller, Peter P.Raitakari, Olli T.Rotter, Jerome I.Rudan, IgorSamani, Nilesh J.Schlessinger, DavidSilva Aldana, Claudia T.Sinner, Moritz F.Smith, Jonathan D.Snieder, HaroldSoliman, Elsayed Z.Spector, Timothy D.Stott, David J.Strauch, KonstantinTarasov, Kirill V.Thorsteinsdottir, UnnurUitterlinden, Andre G.Van Wagoner, David R.Völker, UweVölzke, HenryWaldenberger, MelanieWestra, Harm JanWild, Philipp S.Zeller, TanjaAlonso, AlvaroAvery, Christy L.Bandinelli, StefaniaBenjamin, Emelia J.Cucca, FrancescoDörr, MarcusFerrucci, LuigiGasparini, PaoloORIGINAL9.pdfapplication/pdf2370431https://repository.urosario.edu.co/bitstreams/0ada85e2-8e62-456b-b091-097f0cbc3609/downloade8213d40cd6045670bfa1d708db82d84MD51TEXT9.pdf.txt9.pdf.txtExtracted texttext/plain81885https://repository.urosario.edu.co/bitstreams/e894ea83-cb08-4dbc-9e1f-d0cdce66fbed/download66eabe1e32de57ed49ef86e740dadcc6MD52THUMBNAIL9.pdf.jpg9.pdf.jpgGenerated Thumbnailimage/jpeg3303https://repository.urosario.edu.co/bitstreams/5d89c5fd-f515-4b92-a3a0-8ba530e1bad0/download640af909f5d8c764761068639f3843cbMD5310336/20449oai:repository.urosario.edu.co:10336/204492020-02-12 16:21:11.472https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co

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

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