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

Authors :
Ntalla, I. (Ioanna)
Weng, L.-C.
Cartwright, J.H. (James H.)
Hall, A.W. (Amelia Weber)
Sveinbjornsson, G. (Gardar)
Tucker, N.R. (Nathan R.)
Choi, S.H. (Seung Hoan)
Chaffin, M.D. (Mark D.)
Roselli, C. (Carolina)
Barnes, M.J. (Michael)
Mifsud, B. (Borbala)
Warren, H.R. (Helen R.)
Hayward, C. (Caroline)
Marten, J. (Jonathan)
Cranley, J.J. (James J.)
Concas, M.P. (Maria Pina)
Gasparini, P. (Paolo)
Boutin, T. (Thibaud)
Kolcic, I. (Ivana)
Polasek, O. (Ozren)
Rudan, I. (Igor)
Araujo, N.M. (Nathalia M.)
Lima-Costa, M.F. (Maria Fernanda)
Ribeiro, A.L. (Antonio)
Souza, R.P. (Renan P.)
Tarazona-Santos, E. (Eduardo)
Giedraitis, V. (Vilmantas)
Ingelsson, E. (Erik)
Mahajan, A. (Anubha)
Morris, A.P. (Andrew)
Del Greco M, F. (Fabiola)
Foco, L. (Luisa)
Gögele, M. (Martin)
Hicks, A.A. (Andrew A.)
Cook, J.P. (James P.)
Kao, W.H.L. (Wen)
Lindgren, C.M. (Cecilia M.)
Sundström, J. (Johan)
Nelson, C.P. (Christopher P.)
Riaz, M.B. (Muhammad B.)
Samani, N.J. (Nilesh)
Sinagra, G. (Gianfranco)
Ulivi, S. (Shelia)
Kähönen, M. (Mika)
Mishra, P.P. (Pashupati P.)
Mononen, N. (Nina)
Nikus, K. (Kjell)
Caulfield, M. (Mark)
Dominiczak, A. (Anna)
Padmanabhan, S. (Sandosh)
Montasser, M.E. (May E.)
O’Connell, J.R. (Jeff R.)
Ryan, K. (Kathleen)
Shuldiner, A.R. (Alan R.)
Aeschbacher, S. (Stefanie)
Conen, D. (David)
Risch, L. (Lorenz)
Thériault, S. (Sébastien)
Hutri-Kähönen, N. (Nina)
Lehtimäki, T. (Terho)
Lyytikäinen, L.-P. (Leo-Pekka)
Raitakari, O. (Olli)
Barnes, C.L.K. (Catriona L. K.)
Campbell, H. (Harry)
Joshi, P.K. (Peter)
Wilson, J.F. (James)
Isaacs, A.J. (Aaron)
Kors, J.A. (Jan)
Duijn, C.M. (Cornelia) van
Huang, P.L. (Paul L.)
Gudnason, V. (Vilmundur)
Harris, T.B. (Tamara B.)
Launer, L.J. (Lenore)
Smith, A.V. (Albert)
Bottinger, E.P. (Erwin)
Loos, R.J.F. (Ruth)
Nadkarni, G. (Girish)
Preuss, M. (Michael)
Correa, D.D.
Mei, H. (Hao)
Meitinger, T. (Thomas)
Müller-Nurasyid, M. (Martina)
Peters, A. (Annette)
Waldenberger, M. (Melanie)
Mangino, M. (Massimo)
Spector, T.D. (Timothy)
Rienstra, S.A.
van de Vegte, Y.J. (Yordi J.)
Harst, P. (Pim) van der
Verweij, N. (Niek)
Kääb, S. (Stefan)
Schramm, K. (Katharina)
Sinner, M.F. (Moritz)
Strauch, K. (Konstantin)
Cutler, M.J. (Michael J.)
Fatkin, D. (Diane)
London, B. (Barry)
Olesen, M.S. (Morten S.)
Roden, D.M. (Dan M.)
Benjamin Shoemaker, M. (M.)
Gustav Smith, J. (J.)
Biggs, M.L. (M.)
Bis, J.C. (Joshua)
Brody, J.A. (Jennifer A.)
Psaty, B.M. (Bruce)
Rice, K.M. (Kenneth)
Sotoodehnia, N. (Nona)
Grandi, A. (Alessandro) de
Fuchsberger, C. (Christian)
Penninx, B.W.J.H.
Pramstaller, P.P. (Peter Paul)
Ford, I. (Ian)
Jukema, J.W. (Jan Wouter)
Macfarlane, P.W. (Peter W.)
Trompet, S. (Stella)
Dörr, M. (Marcus)
Felix, S.B. (Stephan B.)
Völker, U. (Uwe)
Weiss, S. (Stefan)
Havulinna, A.S. (Aki)
Jula, A. (Antti)
Sääksjärvi, K. (K.)
Salomaa, V. (Veikko)
Guo, X. (Xiuqing)
Heckbert, S.R. (Susan)
Lin, H.J. (Henry J.)
Rotter, J.I. (Jerome I.)
Taylor, K.D. (Kent)
Yao, J. (Jie)
Mutsert, R. (Reneé) de
Maan, A.C. (Arie C.)
Mook-Kanamori, D.O. (Dennis O.)
Noordam, R. (Raymond)
Cucca, F. (Francesco)
Ding, J. (Jun)
Lakatta, E. (Edward)
Qian, Y. (Yong)
Tarasov, K.V. (Kirill V.)
Levy, D. (Daniel)
Lin, H. (Honghuang)
Newton-Cheh, C. (Christopher)
Lunetta, K.L. (Kathryn)
Murray, A.D. (Alison D.)
Porteous, D.J. (David J.)
Smith, B.H. (Blair)
Stricker, B.H.Ch. (Bruno)
Uitterlinden, A.G. (André)
Berg, M.E. (Marten) van den
Haessler, J. (Jeff)
Jackson, R.D. (Rebecca)
Kooperberg, C. (Charles)
Peters, U. (Ulrike)
Reiner, A.P. (Alexander P.)
Whitsel, E.A. (Eric)
Alonso, A. (Alvaro)
Arking, D.E. (Dan E.)
Boerwinkle, E.A. (Eric)
Ehret, G.B. (Georg B.)
Soliman, E.Z. (Elsayed Z.)
Avery, C.L.
Gogarten, S.M.
Kerr, K.F. (Kathleen)
Laurie, C.C. (Cathy C.)
Seyerle, A.A. (Amanda A.)
Stilp, A. (Adrienne)
Assa, S. (Solmaz)
Abdullah Said, M. (M.)
Yldau van der Ende, M. (M.)
Lambiase, P.D. (Pier)
Orini, M. (Michele)
Ramirez, J. (Julia)
Van Duijvenboden, S. (Stefan)
Arnar, D.O. (David O.)
Gudbjartsson, D.F. (Daniel)
Holm, H. (Hilma)
Sulem, P. (Patrick)
Thorleifsson, G. (Gudmar)
Thorolfsdottir, R.B. (Rosa B.)
Thorsteinsdottir, U. (Unnur)
Benjamin, E.J. (Emelia J.)
Tinker, A. (Andrew)
Zwart, J-A. (John-Anker)
Ellinor, P.T. (Patrick)
Jamshidi, Y. (Yalda)
Lubitz, S.A. (Steven)
Munroe, P. (Patricia)
Ntalla, I. (Ioanna)
Weng, L.-C.
Cartwright, J.H. (James H.)
Hall, A.W. (Amelia Weber)
Sveinbjornsson, G. (Gardar)
Tucker, N.R. (Nathan R.)
Choi, S.H. (Seung Hoan)
Chaffin, M.D. (Mark D.)
Roselli, C. (Carolina)
Barnes, M.J. (Michael)
Mifsud, B. (Borbala)
Warren, H.R. (Helen R.)
Hayward, C. (Caroline)
Marten, J. (Jonathan)
Cranley, J.J. (James J.)
Concas, M.P. (Maria Pina)
Gasparini, P. (Paolo)
Boutin, T. (Thibaud)
Kolcic, I. (Ivana)
Polasek, O. (Ozren)
Rudan, I. (Igor)
Araujo, N.M. (Nathalia M.)
Lima-Costa, M.F. (Maria Fernanda)
Ribeiro, A.L. (Antonio)
Souza, R.P. (Renan P.)
Tarazona-Santos, E. (Eduardo)
Giedraitis, V. (Vilmantas)
Ingelsson, E. (Erik)
Mahajan, A. (Anubha)
Morris, A.P. (Andrew)
Del Greco M, F. (Fabiola)
Foco, L. (Luisa)
Gögele, M. (Martin)
Hicks, A.A. (Andrew A.)
Cook, J.P. (James P.)
Kao, W.H.L. (Wen)
Lindgren, C.M. (Cecilia M.)
Sundström, J. (Johan)
Nelson, C.P. (Christopher P.)
Riaz, M.B. (Muhammad B.)
Samani, N.J. (Nilesh)
Sinagra, G. (Gianfranco)
Ulivi, S. (Shelia)
Kähönen, M. (Mika)
Mishra, P.P. (Pashupati P.)
Mononen, N. (Nina)
Nikus, K. (Kjell)
Caulfield, M. (Mark)
Dominiczak, A. (Anna)
Padmanabhan, S. (Sandosh)
Montasser, M.E. (May E.)
O’Connell, J.R. (Jeff R.)
Ryan, K. (Kathleen)
Shuldiner, A.R. (Alan R.)
Aeschbacher, S. (Stefanie)
Conen, D. (David)
Risch, L. (Lorenz)
Thériault, S. (Sébastien)
Hutri-Kähönen, N. (Nina)
Lehtimäki, T. (Terho)
Lyytikäinen, L.-P. (Leo-Pekka)
Raitakari, O. (Olli)
Barnes, C.L.K. (Catriona L. K.)
Campbell, H. (Harry)
Joshi, P.K. (Peter)
Wilson, J.F. (James)
Isaacs, A.J. (Aaron)
Kors, J.A. (Jan)
Duijn, C.M. (Cornelia) van
Huang, P.L. (Paul L.)
Gudnason, V. (Vilmundur)
Harris, T.B. (Tamara B.)
Launer, L.J. (Lenore)
Smith, A.V. (Albert)
Bottinger, E.P. (Erwin)
Loos, R.J.F. (Ruth)
Nadkarni, G. (Girish)
Preuss, M. (Michael)
Correa, D.D.
Mei, H. (Hao)
Meitinger, T. (Thomas)
Müller-Nurasyid, M. (Martina)
Peters, A. (Annette)
Waldenberger, M. (Melanie)
Mangino, M. (Massimo)
Spector, T.D. (Timothy)
Rienstra, S.A.
van de Vegte, Y.J. (Yordi J.)
Harst, P. (Pim) van der
Verweij, N. (Niek)
Kääb, S. (Stefan)
Schramm, K. (Katharina)
Sinner, M.F. (Moritz)
Strauch, K. (Konstantin)
Cutler, M.J. (Michael J.)
Fatkin, D. (Diane)
London, B. (Barry)
Olesen, M.S. (Morten S.)
Roden, D.M. (Dan M.)
Benjamin Shoemaker, M. (M.)
Gustav Smith, J. (J.)
Biggs, M.L. (M.)
Bis, J.C. (Joshua)
Brody, J.A. (Jennifer A.)
Psaty, B.M. (Bruce)
Rice, K.M. (Kenneth)
Sotoodehnia, N. (Nona)
Grandi, A. (Alessandro) de
Fuchsberger, C. (Christian)
Penninx, B.W.J.H.
Pramstaller, P.P. (Peter Paul)
Ford, I. (Ian)
Jukema, J.W. (Jan Wouter)
Macfarlane, P.W. (Peter W.)
Trompet, S. (Stella)
Dörr, M. (Marcus)
Felix, S.B. (Stephan B.)
Völker, U. (Uwe)
Weiss, S. (Stefan)
Havulinna, A.S. (Aki)
Jula, A. (Antti)
Sääksjärvi, K. (K.)
Salomaa, V. (Veikko)
Guo, X. (Xiuqing)
Heckbert, S.R. (Susan)
Lin, H.J. (Henry J.)
Rotter, J.I. (Jerome I.)
Taylor, K.D. (Kent)
Yao, J. (Jie)
Mutsert, R. (Reneé) de
Maan, A.C. (Arie C.)
Mook-Kanamori, D.O. (Dennis O.)
Noordam, R. (Raymond)
Cucca, F. (Francesco)
Ding, J. (Jun)
Lakatta, E. (Edward)
Qian, Y. (Yong)
Tarasov, K.V. (Kirill V.)
Levy, D. (Daniel)
Lin, H. (Honghuang)
Newton-Cheh, C. (Christopher)
Lunetta, K.L. (Kathryn)
Murray, A.D. (Alison D.)
Porteous, D.J. (David J.)
Smith, B.H. (Blair)
Stricker, B.H.Ch. (Bruno)
Uitterlinden, A.G. (André)
Berg, M.E. (Marten) van den
Haessler, J. (Jeff)
Jackson, R.D. (Rebecca)
Kooperberg, C. (Charles)
Peters, U. (Ulrike)
Reiner, A.P. (Alexander P.)
Whitsel, E.A. (Eric)
Alonso, A. (Alvaro)
Arking, D.E. (Dan E.)
Boerwinkle, E.A. (Eric)
Ehret, G.B. (Georg B.)
Soliman, E.Z. (Elsayed Z.)
Avery, C.L.
Gogarten, S.M.
Kerr, K.F. (Kathleen)
Laurie, C.C. (Cathy C.)
Seyerle, A.A. (Amanda A.)
Stilp, A. (Adrienne)
Assa, S. (Solmaz)
Abdullah Said, M. (M.)
Yldau van der Ende, M. (M.)
Lambiase, P.D. (Pier)
Orini, M. (Michele)
Ramirez, J. (Julia)
Van Duijvenboden, S. (Stefan)
Arnar, D.O. (David O.)
Gudbjartsson, D.F. (Daniel)
Holm, H. (Hilma)
Sulem, P. (Patrick)
Thorleifsson, G. (Gudmar)
Thorolfsdottir, R.B. (Rosa B.)
Thorsteinsdottir, U. (Unnur)
Benjamin, E.J. (Emelia J.)
Tinker, A. (Andrew)
Zwart, J-A. (John-Anker)
Ellinor, P.T. (Patrick)
Jamshidi, Y. (Yalda)
Lubitz, S.A. (Steven)
Munroe, P. (Patricia)
Publication Year :
2020

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 conduc

Details

Database :
OAIster
Notes :
application/pdf, Nature Communications vol. 11 no. 1, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1157012218
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1038.s41467-020-15706-x
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