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

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; 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 Vernon; Steri, Maristella; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; Ulivi, Sheila; Verweij, Niek; Yin, Xiaoyan; Arnar, Davíð 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.; Leach, Irene Mateo; 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.; Þorsteinsdóttir, 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

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dc.contributor	Háskóli Íslands (HÍ)
dc.contributor	University of Iceland (UI)
dc.contributor.author	van Setten, Jessica
dc.contributor.author	Brody, Jennifer A.
dc.contributor.author	Jamshidi, Yalda
dc.contributor.author	Swenson, Brenton R.
dc.contributor.author	Butler, Anne M.
dc.contributor.author	Campbell, Harry
dc.contributor.author	Del Greco, Fabiola M.
dc.contributor.author	Evans, Daniel S.
dc.contributor.author	Gibson, Quince
dc.contributor.author	Gudbjartsson, Daniel
dc.contributor.author	Kerr, Kathleen F.
dc.contributor.author	Krijthe, Bouwe P.
dc.contributor.author	Lyytikäinen, Leo-Pekka
dc.contributor.author	Müller, Christian
dc.contributor.author	Müller-Nurasyid, Martina
dc.contributor.author	Nolte, Ilja M.
dc.contributor.author	Padmanabhan, Sandosh
dc.contributor.author	Ritchie, Marylyn D.
dc.contributor.author	Robino, Antonietta
dc.contributor.author	orcid.org/0000-0003-1942-5845 Smith, Albert Vernon
dc.contributor.author	Steri, Maristella
dc.contributor.author	Tanaka, Toshiko
dc.contributor.author	Teumer, Alexander
dc.contributor.author	Trompet, Stella
dc.contributor.author	Ulivi, Sheila
dc.contributor.author	Verweij, Niek
dc.contributor.author	Yin, Xiaoyan
dc.contributor.author	Arnar, Davíð O.
dc.contributor.author	Asselbergs, Folkert W.
dc.contributor.author	Bader, Joel S.
dc.contributor.author	Barnard, John
dc.contributor.author	Bis, Josh
dc.contributor.author	Blankenberg, Stefan
dc.contributor.author	Boerwinkle, Eric
dc.contributor.author	Bradford, Yuki
dc.contributor.author	Buckley, Brendan M.
dc.contributor.author	Chung, Mina K.
dc.contributor.author	Crawford, Dana
dc.contributor.author	den Hoed, Marcel
dc.contributor.author	Denny, Josh C.
dc.contributor.author	Dominiczak, Anna F.
dc.contributor.author	Ehret, Georg B.
dc.contributor.author	Eijgelsheim, Mark
dc.contributor.author	Ellinor, Patrick T.
dc.contributor.author	Felix, Stephan B.
dc.contributor.author	Franco, Oscar H.
dc.contributor.author	Franke, Lude
dc.contributor.author	Harris, Tamara B.
dc.contributor.author	orcid.org/0000-0002-9517-6636 Holm, Hilma
dc.contributor.author	Ilaria, Gandin
dc.contributor.author	Iorio, Annamaria
dc.contributor.author	Kähönen, Mika
dc.contributor.author	Kolcic, Ivana
dc.contributor.author	Kors, Jan A.
dc.contributor.author	Lakatta, Edward G.
dc.contributor.author	Launer, Lenore J.
dc.contributor.author	Lin, Honghuang
dc.contributor.author	Lin, Henry J.
dc.contributor.author	Loos, Ruth J. F.
dc.contributor.author	Lubitz, Steven A.
dc.contributor.author	Macfarlane, Peter W.
dc.contributor.author	Magnani, Jared W.
dc.contributor.author	Leach, Irene Mateo
dc.contributor.author	Meitinger, Thomas
dc.contributor.author	Mitchell, Braxton D.
dc.contributor.author	Munzel, Thomas
dc.contributor.author	Papanicolaou, George J.
dc.contributor.author	Peters, Annette
dc.contributor.author	Pfeufer, Arne
dc.contributor.author	Pramstaller, Peter P.
dc.contributor.author	Raitakari, Olli T.
dc.contributor.author	Rotter, Jerome I.
dc.contributor.author	Rudan, Igor
dc.contributor.author	Samani, Nilesh J.
dc.contributor.author	Schlessinger, David
dc.contributor.author	Silva Aldana, Claudia T.
dc.contributor.author	Sinner, Moritz F.
dc.contributor.author	Smith, Jonathan D.
dc.contributor.author	Snieder, Harold
dc.contributor.author	Soliman, Elsayed Z.
dc.contributor.author	Spector, Timothy D.
dc.contributor.author	Stott, David J.
dc.contributor.author	Strauch, Konstantin
dc.contributor.author	Tarasov, Kirill V.
dc.contributor.author	Þorsteinsdóttir, Unnur
dc.contributor.author	Uitterlinden, Andre G.
dc.contributor.author	Van Wagoner, David R.
dc.contributor.author	Völker, Uwe
dc.contributor.author	Völzke, Henry
dc.contributor.author	Waldenberger, Melanie
dc.contributor.author	Jan Westra, Harm
dc.contributor.author	Wild, Philipp S.
dc.contributor.author	Zeller, Tanja
dc.contributor.author	Alonso, Alvaro
dc.contributor.author	Avery, Christy L.
dc.contributor.author	Bandinelli, Stefania
dc.contributor.author	Benjamin, Emelia J.
dc.contributor.author	Cucca, Francesco
dc.contributor.author	Dörr, Marcus
dc.contributor.author	Ferrucci, Luigi
dc.contributor.author	Gasparini, Paolo
dc.contributor.author	orcid.org/0000-0001-5696-0084 Gudnason, Vilmundur
dc.contributor.author	Hayward, Caroline
dc.contributor.author	Heckbert, Susan R.
dc.contributor.author	Hicks, Andrew A.
dc.contributor.author	Jukema, J. Wouter
dc.contributor.author	Kääb, Stefan
dc.contributor.author	Lehtimäki, Terho
dc.contributor.author	Liu, Yongmei
dc.contributor.author	Munroe, Patricia B.
dc.contributor.author	Parsa, Afshin
dc.contributor.author	Polasek, Ozren
dc.contributor.author	Psaty, Bruce M.
dc.contributor.author	Roden, Dan M.
dc.contributor.author	Schnabel, Renate B.
dc.contributor.author	Sinagra, Gianfranco
dc.contributor.author	orcid.org/0000-0003-1676-864X Stefansson, Kari
dc.contributor.author	Stricker, Bruno H.
dc.contributor.author	van der Harst, Pim
dc.contributor.author	van Duijn, Cornelia M.
dc.contributor.author	Wilson, James F.
dc.contributor.author	Gharib, Sina A.
dc.contributor.author	de Bakker, Paul I. W.
dc.contributor.author	Isaacs, Aaron
dc.contributor.author	Arking, Dan E.
dc.contributor.author	Sotoodehnia, Nona
dc.date.accessioned	2019-12-16T11:33:23Z
dc.date.available	2019-12-16T11:33:23Z
dc.date.issued	2018-07-25
dc.identifier.citation	van 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/s41467-018-04766-9
dc.identifier.issn	2041-1723
dc.identifier.uri	https://hdl.handle.net/20.500.11815/1392
dc.description	Publisher's version (útgefin grein). Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
dc.description.abstract	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.
dc.description.sponsorship	Acknowledgements 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.
dc.format.extent	2904
dc.language.iso	en
dc.publisher	Springer Science and Business Media LLC
dc.relation.ispartofseries	Nature Communications;9(1)
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Atrial Fibrillation
dc.subject	Heart Diseases
dc.subject	Heart Block
dc.subject	Genome-Wide Association Study
dc.subject	Cardiovascular genetics
dc.title	PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
dc.type	info:eu-repo/semantics/article
dcterms.license	Open 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/.
dc.description.version	Peer Reviewed
dc.identifier.journal	Nature Communications
dc.identifier.doi	10.1038/s41467-018-04766-9
dc.contributor.department	Faculty of Medicine (UI)
dc.contributor.department	Læknadeild (HÍ)
dc.contributor.school	School of Engineering and Natural Sciences (UI)
dc.contributor.school	Verkfræði- og náttúruvísindasvið (HÍ)
dc.contributor.school	School of Health Sciences (UI)
dc.contributor.school	Heilbrigðisvísindasvið (HÍ)