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

Ntalla, Ioanna; Weng, Lu-Chen; Cartwright, James H.; Hall, Amelia Weber; Sveinbjornsson, Gardar; Tucker, Nathan R.; Choi, Seung Hoan; Chaffin, Mark D.; Roselli, Carolina; Barnes, Michael R.; Mifsud, Borbala; Warren, Helen R.; Hayward, Caroline; Marten, Jonathan; Cranley, James J.; Concas, Maria Pina; Gasparini, Paolo; Boutin, Thibaud; Kolcic, Ivana; Polasek, Ozren; Rudan, Igor; Araujo, Nathalia M.; Lima-Costa, Maria Fernanda; Ribeiro, Antonio Luiz P.; Souza, Renan P.; Tarazona-Santos, Eduardo; Giedraitis, Vilmantas; Ingelsson, Erik; Mahajan, Anubha; Morris, Andrew P.; Del Greco M, Fabiola; Foco, Luisa; Gögele, Martin; Hicks, Andrew A.; Cook, James P.; Lind, Lars; Lindgren, Cecilia M.; Sundström, Johan; Nelson, Christopher P.; Riaz, Muhammad B.; Samani, Nilesh J.; Sinagra, Gianfranco; Ulivi, Sheila; Kähönen, Mika; Mishra, Pashupati P.; Mononen, Nina; Nikus, Kjell; Caulfield, Mark J.; Dominiczak, Anna; Padmanabhan, Sandosh; Montasser, May E.; O’Connell, Jeff R.; Ryan, Kathleen; Shuldiner, Alan R.; Aeschbacher, Stefanie; Conen, David; Risch, Lorenz; Thériault, Sébastien; Hutri-Kähönen, Nina; Lehtimäki, Terho; Lyytikäinen, Leo-Pekka; Raitakari, Olli T.; Barnes, Catriona L. K.; Campbell, Harry; Joshi, Peter K.; Wilson, James F.; Isaacs, Aaron; Kors, Jan A.; van Duijn, Cornelia M.; Huang, Paul L.; Gudnason, Vilmundur; Harris, Tamara B.; Launer, Lenore J.; Smith, Albert Vernon; Bottinger, Erwin P.; Loos, Ruth J. F.; Nadkarni, Girish N.; Preuss, Michael H.; Correa, Adolfo; Mei, Hao; Wilson, James; Meitinger, Thomas; Müller-Nurasyid, Martina; Peters, Annette; Waldenberger, Melanie; Mangino, Massimo; Spector, Timothy D.; Rienstra, Michiel; van de Vegte, Yordi J.; van der Harst, Pim; Verweij, Niek; Kääb, Stefan; Schramm, Katharina; Sinner, Moritz F.; Strauch, Konstantin; Cutler, Michael J.; Fatkin, Diane; London, Barry; Olesen, Morten; Roden, Dan M.; Benjamin Shoemaker, M.; Gustav Smith, J.; Biggs, Mary L.; Bis, Joshua C.; Brody, Jennifer A.; Psaty, Bruce M.; Rice, Kenneth; Sotoodehnia, Nona; De Grandi, Alessandro; Fuchsberger, Christian; Pattaro, Cristian; Pramstaller, Peter P.; Ford, Ian; Wouter Jukema, J.; Macfarlane, Peter W.; Trompet, Stella; Dörr, Marcus; Felix, Stephan B.; Völker, Uwe; Weiss, Stefan; Havulinna, Aki S.; Jula, Antti; Sääksjärvi, Katri; Salomaa, Veikko; Guo, Xiuqing; Heckbert, Susan R.; Lin, Henry J.; Rotter, Jerome I.; Taylor, Kent D.; Yao, Jie; de Mutsert, Renée; Maan, Arie C.; Mook-Kanamori, Dennis O.; Noordam, Raymond; Cucca, Francesco; Ding, Jun; Lakatta, Edward G.; Qian, Yong; Tarasov, Kirill V.; Levy, Daniel; Lin, Honghuang; Newton-Cheh, Christopher H.; Lunetta, Kathryn L.; Murray, Alison D.; Porteous, David J.; Smith, Blair H.; Stricker, Bruno H.; Uitterlinden, André; van den Berg, Marten E.; Haessler, Jeffrey; Jackson, Rebecca D.; Kooperberg, Charles; Peters, Ulrike; Reiner, Alexander P.; Whitsel, Eric A.; Alonso, Alvaro; Arking, Dan E.; Boerwinkle, Eric; Ehret, Georg B.; Soliman, Elsayed Z.; Avery, Christy L.; Gogarten, Stephanie M.; Kerr, Kathleen F.; Laurie, Cathy C.; Seyerle, Amanda A.; Stilp, Adrienne; Assa, Solmaz; Abdullah Said, M.; Yldau van der Ende, M.; Lambiase, Pier D.; Orini, Michele; Ramirez, Julia; Van Duijvenboden, Stefan; Arnar, Davíð O.; Gudbjartsson, Daniel; Holm, Hilma; sulem, patrick; Thorleifsson, Gudmar; Thorolfsdottir, Rosa B; Thorsteinsdottir, Unnur; Benjamin, Emelia J.; Tinker, Andrew; Stefansson, Kari; Ellinor, Patrick T.; Jamshidi, Yalda; Lubitz, Steven A.; Munroe, Patricia B.

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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	orcid.org/0000-0003-2429-9468 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	orcid.org/0000-0001-5696-0084 Gudnason, Vilmundur
dc.contributor.author	Harris, Tamara B.
dc.contributor.author	Launer, Lenore J.
dc.contributor.author	orcid.org/0000-0003-1942-5845 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	orcid.org/0000-0002-9517-6636 Holm, Hilma
dc.contributor.author	orcid.org/0000-0001-7123-6123 sulem, patrick
dc.contributor.author	orcid.org/0000-0003-4623-9087 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	orcid.org/0000-0003-1676-864X Stefansson, Kari
dc.contributor.author	Ellinor, Patrick T.
dc.contributor.author	orcid.org/0000-0003-0151-6482 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)