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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Ntalla, Ioanna
dc.contributor.author Weng, Lu-Chen
dc.contributor.author Cartwright, James H.
dc.contributor.author Hall, Amelia Weber
dc.contributor.author Sveinbjornsson, Gardar
dc.contributor.author Tucker, Nathan R.
dc.contributor.author Choi, Seung Hoan
dc.contributor.author Chaffin, Mark D.
dc.contributor.author Roselli, Carolina
dc.contributor.author Barnes, Michael R.
dc.contributor.author Mifsud, Borbala
dc.contributor.author Warren, Helen R.
dc.contributor.author Hayward, Caroline
dc.contributor.author Marten, Jonathan
dc.contributor.author Cranley, James J.
dc.contributor.author Concas, Maria Pina
dc.contributor.author Gasparini, Paolo
dc.contributor.author Boutin, Thibaud
dc.contributor.author Kolcic, Ivana
dc.contributor.author Polasek, Ozren
dc.contributor.author Rudan, Igor
dc.contributor.author Araujo, Nathalia M.
dc.contributor.author Lima-Costa, Maria Fernanda
dc.contributor.author Ribeiro, Antonio Luiz P.
dc.contributor.author Souza, Renan P.
dc.contributor.author Tarazona-Santos, Eduardo
dc.contributor.author Giedraitis, Vilmantas
dc.contributor.author Ingelsson, Erik
dc.contributor.author Mahajan, Anubha
dc.contributor.author Morris, Andrew P.
dc.contributor.author Del Greco M, Fabiola
dc.contributor.author Foco, Luisa
dc.contributor.author Gögele, Martin
dc.contributor.author Hicks, Andrew A.
dc.contributor.author Cook, James P.
dc.contributor.author Lind, Lars
dc.contributor.author Lindgren, Cecilia M.
dc.contributor.author Sundström, Johan
dc.contributor.author Nelson, Christopher P.
dc.contributor.author Riaz, Muhammad B.
dc.contributor.author Samani, Nilesh J.
dc.contributor.author Sinagra, Gianfranco
dc.contributor.author Ulivi, Sheila
dc.contributor.author Kähönen, Mika
dc.contributor.author Mishra, Pashupati P.
dc.contributor.author Mononen, Nina
dc.contributor.author Nikus, Kjell
dc.contributor.author Caulfield, Mark J.
dc.contributor.author Dominiczak, Anna
dc.contributor.author Padmanabhan, Sandosh
dc.contributor.author Montasser, May E.
dc.contributor.author O’Connell, Jeff R.
dc.contributor.author Ryan, Kathleen
dc.contributor.author Shuldiner, Alan R.
dc.contributor.author Aeschbacher, Stefanie
dc.contributor.author Conen, David
dc.contributor.author Risch, Lorenz
dc.contributor.author Thériault, Sébastien
dc.contributor.author Hutri-Kähönen, Nina
dc.contributor.author Lehtimäki, Terho
dc.contributor.author Lyytikäinen, Leo-Pekka
dc.contributor.author Raitakari, Olli T.
dc.contributor.author Barnes, Catriona L. K.
dc.contributor.author Campbell, Harry
dc.contributor.author Joshi, Peter K.
dc.contributor.author Wilson, James F.
dc.contributor.author Isaacs, Aaron
dc.contributor.author Kors, Jan A.
dc.contributor.author van Duijn, Cornelia M.
dc.contributor.author Huang, Paul L.
dc.contributor.author Gudnason, Vilmundur
dc.contributor.author Harris, Tamara B.
dc.contributor.author Launer, Lenore J.
dc.contributor.author Smith, Albert Vernon
dc.contributor.author Bottinger, Erwin P.
dc.contributor.author Loos, Ruth J. F.
dc.contributor.author Nadkarni, Girish N.
dc.contributor.author Preuss, Michael H.
dc.contributor.author Correa, Adolfo
dc.contributor.author Mei, Hao
dc.contributor.author Wilson, James
dc.contributor.author Meitinger, Thomas
dc.contributor.author Müller-Nurasyid, Martina
dc.contributor.author Peters, Annette
dc.contributor.author Waldenberger, Melanie
dc.contributor.author Mangino, Massimo
dc.contributor.author Spector, Timothy D.
dc.contributor.author Rienstra, Michiel
dc.contributor.author van de Vegte, Yordi J.
dc.contributor.author van der Harst, Pim
dc.contributor.author Verweij, Niek
dc.contributor.author Kääb, Stefan
dc.contributor.author Schramm, Katharina
dc.contributor.author Sinner, Moritz F.
dc.contributor.author Strauch, Konstantin
dc.contributor.author Cutler, Michael J.
dc.contributor.author Fatkin, Diane
dc.contributor.author London, Barry
dc.contributor.author Olesen, Morten
dc.contributor.author Roden, Dan M.
dc.contributor.author Benjamin Shoemaker, M.
dc.contributor.author Gustav Smith, J.
dc.contributor.author Biggs, Mary L.
dc.contributor.author Bis, Joshua C.
dc.contributor.author Brody, Jennifer A.
dc.contributor.author Psaty, Bruce M.
dc.contributor.author Rice, Kenneth
dc.contributor.author Sotoodehnia, Nona
dc.contributor.author De Grandi, Alessandro
dc.contributor.author Fuchsberger, Christian
dc.contributor.author Pattaro, Cristian
dc.contributor.author Pramstaller, Peter P.
dc.contributor.author Ford, Ian
dc.contributor.author Wouter Jukema, J.
dc.contributor.author Macfarlane, Peter W.
dc.contributor.author Trompet, Stella
dc.contributor.author Dörr, Marcus
dc.contributor.author Felix, Stephan B.
dc.contributor.author Völker, Uwe
dc.contributor.author Weiss, Stefan
dc.contributor.author Havulinna, Aki S.
dc.contributor.author Jula, Antti
dc.contributor.author Sääksjärvi, Katri
dc.contributor.author Salomaa, Veikko
dc.contributor.author Guo, Xiuqing
dc.contributor.author Heckbert, Susan R.
dc.contributor.author Lin, Henry J.
dc.contributor.author Rotter, Jerome I.
dc.contributor.author Taylor, Kent D.
dc.contributor.author Yao, Jie
dc.contributor.author de Mutsert, Renée
dc.contributor.author Maan, Arie C.
dc.contributor.author Mook-Kanamori, Dennis O.
dc.contributor.author Noordam, Raymond
dc.contributor.author Cucca, Francesco
dc.contributor.author Ding, Jun
dc.contributor.author Lakatta, Edward G.
dc.contributor.author Qian, Yong
dc.contributor.author Tarasov, Kirill V.
dc.contributor.author Levy, Daniel
dc.contributor.author Lin, Honghuang
dc.contributor.author Newton-Cheh, Christopher H.
dc.contributor.author Lunetta, Kathryn L.
dc.contributor.author Murray, Alison D.
dc.contributor.author Porteous, David J.
dc.contributor.author Smith, Blair H.
dc.contributor.author Stricker, Bruno H.
dc.contributor.author Uitterlinden, André
dc.contributor.author van den Berg, Marten E.
dc.contributor.author Haessler, Jeffrey
dc.contributor.author Jackson, Rebecca D.
dc.contributor.author Kooperberg, Charles
dc.contributor.author Peters, Ulrike
dc.contributor.author Reiner, Alexander P.
dc.contributor.author Whitsel, Eric A.
dc.contributor.author Alonso, Alvaro
dc.contributor.author Arking, Dan E.
dc.contributor.author Boerwinkle, Eric
dc.contributor.author Ehret, Georg B.
dc.contributor.author Soliman, Elsayed Z.
dc.contributor.author Avery, Christy L.
dc.contributor.author Gogarten, Stephanie M.
dc.contributor.author Kerr, Kathleen F.
dc.contributor.author Laurie, Cathy C.
dc.contributor.author Seyerle, Amanda A.
dc.contributor.author Stilp, Adrienne
dc.contributor.author Assa, Solmaz
dc.contributor.author Abdullah Said, M.
dc.contributor.author Yldau van der Ende, M.
dc.contributor.author Lambiase, Pier D.
dc.contributor.author Orini, Michele
dc.contributor.author Ramirez, Julia
dc.contributor.author Van Duijvenboden, Stefan
dc.contributor.author Arnar, Davíð O.
dc.contributor.author Gudbjartsson, Daniel
dc.contributor.author Holm, Hilma
dc.contributor.author sulem, patrick
dc.contributor.author Thorleifsson, Gudmar
dc.contributor.author Thorolfsdottir, Rosa B
dc.contributor.author Thorsteinsdottir, Unnur
dc.contributor.author Benjamin, Emelia J.
dc.contributor.author Tinker, Andrew
dc.contributor.author Stefansson, Kari
dc.contributor.author Ellinor, Patrick T.
dc.contributor.author Jamshidi, Yalda
dc.contributor.author Lubitz, Steven A.
dc.contributor.author Munroe, Patricia B.
dc.date.accessioned 2020-10-30T09:54:33Z
dc.date.available 2020-10-30T09:54:33Z
dc.date.issued 2020-05-21
dc.identifier.citation Ntalla, I., Weng, L., Cartwright, J.H. et al. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction. Nature Communications 11, 2542 (2020). https://doi.org/10.1038/s41467-020-15706-x
dc.identifier.issn 2041-1723
dc.identifier.uri https://hdl.handle.net/20.500.11815/2149
dc.description Publisher's version (útgefin grein)
dc.description.abstract The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
dc.description.sponsorship We provide all investigator and study-specific acknowledgements in Supplementary Note 1, and funding sources in Supplementary Note 2.
dc.format.extent 2542
dc.language.iso en
dc.publisher Springer Science and Business Media LLC
dc.relation.ispartofseries Nature Communications;11(1)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Multi-ancestry GWAS
dc.subject Electrocardiography
dc.subject Cardiovascular Diseases
dc.subject Erfðarannsóknir
dc.subject Arfgengi
dc.subject Blóðrásarsjúkdómar
dc.title Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
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/s41467-020-15706-x
dc.relation.url https://www.nature.com/articles/s41467-020-15706-x
dc.contributor.department Læknadeild (HÍ)
dc.contributor.department Faculty of Medicine (UI)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)
dc.contributor.school Verkfræði- og náttúruvísindasvið (HÍ)
dc.contributor.school School of Engineering and Natural Sciences (UI)


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