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

Almenn færsla
dc.contributorHáskóli Íslandsen_US
dc.contributorUniversity of Icelanden_US
dc.contributor.authorNtalla, Ioanna
dc.contributor.authorWeng, Lu-Chen
dc.contributor.authorCartwright, James H.
dc.contributor.authorHall, Amelia Weber
dc.contributor.authorSveinbjornsson, Gardar
dc.contributor.authorTucker, Nathan R.
dc.contributor.authorChoi, Seung Hoan
dc.contributor.authorChaffin, Mark D.
dc.contributor.authorRoselli, Carolina
dc.contributor.authorBarnes, Michael R.
dc.contributor.authorMifsud, Borbala
dc.contributor.authorWarren, Helen R.
dc.contributor.authorHayward, Caroline
dc.contributor.authorMarten, Jonathan
dc.contributor.authorCranley, James J.
dc.contributor.authorConcas, Maria Pina
dc.contributor.authorGasparini, Paolo
dc.contributor.authorBoutin, Thibaud
dc.contributor.authorKolcic, Ivana
dc.contributor.authorPolasek, Ozren
dc.contributor.authorRudan, Igor
dc.contributor.authorAraujo, Nathalia M.
dc.contributor.authorLima-Costa, Maria Fernanda
dc.contributor.authorRibeiro, Antonio Luiz P.
dc.contributor.authorSouza, Renan P.
dc.contributor.authorTarazona-Santos, Eduardo
dc.contributor.authorGiedraitis, Vilmantas
dc.contributor.authorIngelsson, Erik
dc.contributor.authorMahajan, Anubha
dc.contributor.authorMorris, Andrew P.
dc.contributor.authorDel Greco M, Fabiola
dc.contributor.authorFoco, Luisa
dc.contributor.authorGögele, Martin
dc.contributor.authorHicks, Andrew A.
dc.contributor.authorCook, James P.
dc.contributor.authorLind, Lars
dc.contributor.authorLindgren, Cecilia M.
dc.contributor.authorSundström, Johan
dc.contributor.authorNelson, Christopher P.
dc.contributor.authorRiaz, Muhammad B.
dc.contributor.authorSamani, Nilesh J.
dc.contributor.authorSinagra, Gianfranco
dc.contributor.authorUlivi, Sheila
dc.contributor.authorKähönen, Mika
dc.contributor.authorMishra, Pashupati P.
dc.contributor.authorMononen, Nina
dc.contributor.authorNikus, Kjell
dc.contributor.authorCaulfield, Mark J.
dc.contributor.authorDominiczak, Anna
dc.contributor.authorPadmanabhan, Sandosh
dc.contributor.authorMontasser, May E.
dc.contributor.authorO’Connell, Jeff R.
dc.contributor.authorRyan, Kathleen
dc.contributor.authorShuldiner, Alan R.
dc.contributor.authorAeschbacher, Stefanie
dc.contributor.authorConen, David
dc.contributor.authorRisch, Lorenz
dc.contributor.authorThériault, Sébastien
dc.contributor.authorHutri-Kähönen, Nina
dc.contributor.authorLehtimäki, Terho
dc.contributor.authorLyytikäinen, Leo-Pekka
dc.contributor.authorRaitakari, Olli T.
dc.contributor.authorBarnes, Catriona L. K.
dc.contributor.authorCampbell, Harry
dc.contributor.authorJoshi, Peter K.
dc.contributor.authorWilson, James F.
dc.contributor.authorIsaacs, Aaron
dc.contributor.authorKors, Jan A.
dc.contributor.authorvan Duijn, Cornelia M.
dc.contributor.authorHuang, Paul L.
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorHarris, Tamara B.
dc.contributor.authorLauner, Lenore J.
dc.contributor.authorSmith, Albert Vernon
dc.contributor.authorBottinger, Erwin P.
dc.contributor.authorLoos, Ruth J. F.
dc.contributor.authorNadkarni, Girish N.
dc.contributor.authorPreuss, Michael H.
dc.contributor.authorCorrea, Adolfo
dc.contributor.authorMei, Hao
dc.contributor.authorWilson, James
dc.contributor.authorMeitinger, Thomas
dc.contributor.authorMüller-Nurasyid, Martina
dc.contributor.authorPeters, Annette
dc.contributor.authorWaldenberger, Melanie
dc.contributor.authorMangino, Massimo
dc.contributor.authorSpector, Timothy D.
dc.contributor.authorRienstra, Michiel
dc.contributor.authorvan de Vegte, Yordi J.
dc.contributor.authorvan der Harst, Pim
dc.contributor.authorVerweij, Niek
dc.contributor.authorKääb, Stefan
dc.contributor.authorSchramm, Katharina
dc.contributor.authorSinner, Moritz F.
dc.contributor.authorStrauch, Konstantin
dc.contributor.authorCutler, Michael J.
dc.contributor.authorFatkin, Diane
dc.contributor.authorLondon, Barry
dc.contributor.authorOlesen, Morten
dc.contributor.authorRoden, Dan M.
dc.contributor.authorBenjamin Shoemaker, M.
dc.contributor.authorGustav Smith, J.
dc.contributor.authorBiggs, Mary L.
dc.contributor.authorBis, Joshua C.
dc.contributor.authorBrody, Jennifer A.
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorRice, Kenneth
dc.contributor.authorSotoodehnia, Nona
dc.contributor.authorDe Grandi, Alessandro
dc.contributor.authorFuchsberger, Christian
dc.contributor.authorPattaro, Cristian
dc.contributor.authorPramstaller, Peter P.
dc.contributor.authorFord, Ian
dc.contributor.authorWouter Jukema, J.
dc.contributor.authorMacfarlane, Peter W.
dc.contributor.authorTrompet, Stella
dc.contributor.authorDörr, Marcus
dc.contributor.authorFelix, Stephan B.
dc.contributor.authorVölker, Uwe
dc.contributor.authorWeiss, Stefan
dc.contributor.authorHavulinna, Aki S.
dc.contributor.authorJula, Antti
dc.contributor.authorSääksjärvi, Katri
dc.contributor.authorSalomaa, Veikko
dc.contributor.authorGuo, Xiuqing
dc.contributor.authorHeckbert, Susan R.
dc.contributor.authorLin, Henry J.
dc.contributor.authorRotter, Jerome I.
dc.contributor.authorTaylor, Kent D.
dc.contributor.authorYao, Jie
dc.contributor.authorde Mutsert, Renée
dc.contributor.authorMaan, Arie C.
dc.contributor.authorMook-Kanamori, Dennis O.
dc.contributor.authorNoordam, Raymond
dc.contributor.authorCucca, Francesco
dc.contributor.authorDing, Jun
dc.contributor.authorLakatta, Edward G.
dc.contributor.authorQian, Yong
dc.contributor.authorTarasov, Kirill V.
dc.contributor.authorLevy, Daniel
dc.contributor.authorLin, Honghuang
dc.contributor.authorNewton-Cheh, Christopher H.
dc.contributor.authorLunetta, Kathryn L.
dc.contributor.authorMurray, Alison D.
dc.contributor.authorPorteous, David J.
dc.contributor.authorSmith, Blair H.
dc.contributor.authorStricker, Bruno H.
dc.contributor.authorUitterlinden, André
dc.contributor.authorvan den Berg, Marten E.
dc.contributor.authorHaessler, Jeffrey
dc.contributor.authorJackson, Rebecca D.
dc.contributor.authorKooperberg, Charles
dc.contributor.authorPeters, Ulrike
dc.contributor.authorReiner, Alexander P.
dc.contributor.authorWhitsel, Eric A.
dc.contributor.authorAlonso, Alvaro
dc.contributor.authorArking, Dan E.
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorEhret, Georg B.
dc.contributor.authorSoliman, Elsayed Z.
dc.contributor.authorAvery, Christy L.
dc.contributor.authorGogarten, Stephanie M.
dc.contributor.authorKerr, Kathleen F.
dc.contributor.authorLaurie, Cathy C.
dc.contributor.authorSeyerle, Amanda A.
dc.contributor.authorStilp, Adrienne
dc.contributor.authorAssa, Solmaz
dc.contributor.authorAbdullah Said, M.
dc.contributor.authorYldau van der Ende, M.
dc.contributor.authorLambiase, Pier D.
dc.contributor.authorOrini, Michele
dc.contributor.authorRamirez, Julia
dc.contributor.authorVan Duijvenboden, Stefan
dc.contributor.authorArnar, Davíð O.
dc.contributor.authorGudbjartsson, Daniel
dc.contributor.authorHolm, Hilma
dc.contributor.authorsulem, patrick
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorThorolfsdottir, Rosa B
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorBenjamin, Emelia J.
dc.contributor.authorTinker, Andrew
dc.contributor.authorStefansson, Kari
dc.contributor.authorEllinor, Patrick T.
dc.contributor.authorJamshidi, Yalda
dc.contributor.authorLubitz, Steven A.
dc.contributor.authorMunroe, Patricia B.
dc.contributor.departmentLæknadeild (HÍ)en_US
dc.contributor.departmentFaculty of Medicine (UI)en_US
dc.contributor.schoolHeilbrigðisvísindasvið (HÍ)en_US
dc.contributor.schoolSchool of Health Sciences (UI)en_US
dc.contributor.schoolVerkfræði- og náttúruvísindasvið (HÍ)en_US
dc.contributor.schoolSchool of Engineering and Natural Sciences (UI)en_US
dc.date.accessioned2020-10-30T09:54:33Z
dc.date.available2020-10-30T09:54:33Z
dc.date.issued2020-05-21
dc.descriptionPublisher's version (útgefin grein)en_US
dc.description.abstractThe 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.en_US
dc.description.sponsorshipWe provide all investigator and study-specific acknowledgements in Supplementary Note 1, and funding sources in Supplementary Note 2.en_US
dc.description.versionPeer Revieweden_US
dc.format.extent2542en_US
dc.identifier.citationNtalla, 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-xen_US
dc.identifier.doi10.1038/s41467-020-15706-x
dc.identifier.issn2041-1723
dc.identifier.journalNature Communicationsen_US
dc.identifier.urihttps://hdl.handle.net/20.500.11815/2149
dc.language.isoenen_US
dc.publisherSpringer Science and Business Media LLCen_US
dc.relation.ispartofseriesNature Communications;11(1)
dc.relation.urlhttps://www.nature.com/articles/s41467-020-15706-xen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectMulti-ancestry GWASen_US
dc.subjectElectrocardiographyen_US
dc.subjectCardiovascular Diseasesen_US
dc.subjectErfðarannsókniren_US
dc.subjectArfgengien_US
dc.subjectBlóðrásarsjúkdómaren_US
dc.titleMulti-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conductionen_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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