Standard
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 V.; 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, David O.; Gudbjartsson, Daniel F.; 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.
In:
Nature Communications, Vol. 11, No. 1, 2542, 01.12.2020.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Ntalla, I, Weng, LC, Cartwright, JH, Hall, AW, Sveinbjornsson, G, Tucker, NR, Choi, SH, Chaffin, MD, Roselli, C, Barnes, MR, Mifsud, B, Warren, HR, Hayward, C, Marten, J, Cranley, JJ, Concas, MP, Gasparini, P, Boutin, T, Kolcic, I, Polasek, O, Rudan, I, Araujo, NM, Lima-Costa, MF, Ribeiro, ALP, Souza, RP, Tarazona-Santos, E, Giedraitis, V, Ingelsson, E, Mahajan, A, Morris, AP, Del Greco M, F, Foco, L, Gögele, M, Hicks, AA, Cook, JP, Lind, L, Lindgren, CM, Sundström, J, Nelson, CP, Riaz, MB, Samani, NJ, Sinagra, G, Ulivi, S, Kähönen, M, Mishra, PP, Mononen, N, Nikus, K, Caulfield, MJ, Dominiczak, A, Padmanabhan, S, Montasser, ME, O’Connell, JR, Ryan, K, Shuldiner, AR, Aeschbacher, S, Conen, D, Risch, L, Thériault, S, Hutri-Kähönen, N, Lehtimäki, T, Lyytikäinen, LP, Raitakari, OT, Barnes, CLK, Campbell, H, Joshi, PK, Wilson, JF, Isaacs, A, Kors, JA, van Duijn, CM, Huang, PL, Gudnason, V, Harris, TB, Launer, LJ, Smith, AV, Bottinger, EP
, Loos, RJF, Nadkarni, GN, Preuss, MH, Correa, A, Mei, H, Wilson, J, Meitinger, T, Müller-Nurasyid, M, Peters, A, Waldenberger, M, Mangino, M, Spector, TD, Rienstra, M, van de Vegte, YJ, van der Harst, P, Verweij, N, Kääb, S, Schramm, K, Sinner, MF, Strauch, K, Cutler, MJ, Fatkin, D, London, B
, Olesen, M, Roden, DM, Benjamin Shoemaker, M, Gustav Smith, J, Biggs, ML, Bis, JC, Brody, JA, Psaty, BM, Rice, K, Sotoodehnia, N, De Grandi, A, Fuchsberger, C, Pattaro, C, Pramstaller, PP, Ford, I, Wouter Jukema, J, Macfarlane, PW, Trompet, S, Dörr, M, Felix, SB, Völker, U, Weiss, S, Havulinna, AS, Jula, A, Sääksjärvi, K, Salomaa, V, Guo, X, Heckbert, SR, Lin, HJ, Rotter, JI, Taylor, KD, Yao, J, de Mutsert, R, Maan, AC, Mook-Kanamori, DO, Noordam, R, Cucca, F, Ding, J, Lakatta, EG, Qian, Y, Tarasov, KV, Levy, D, Lin, H, Newton-Cheh, CH, Lunetta, KL, Murray, AD, Porteous, DJ, Smith, BH, Stricker, BH, Uitterlinden, A, van den Berg, ME, Haessler, J, Jackson, RD, Kooperberg, C, Peters, U, Reiner, AP, Whitsel, EA, Alonso, A, Arking, DE, Boerwinkle, E, Ehret, GB, Soliman, EZ, Avery, CL, Gogarten, SM, Kerr, KF, Laurie, CC, Seyerle, AA, Stilp, A, Assa, S, Abdullah Said, M, Yldau van der Ende, M, Lambiase, PD, Orini, M, Ramirez, J, Van Duijvenboden, S, Arnar, DO, Gudbjartsson, DF, Holm, H, Sulem, P, Thorleifsson, G, Thorolfsdottir, RB, Thorsteinsdottir, U, Benjamin, EJ, Tinker, A, Stefansson, K, Ellinor, PT, Jamshidi, Y, Lubitz, SA & Munroe, PB 2020, '
Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction',
Nature Communications, vol. 11, no. 1, 2542.
https://doi.org/10.1038/s41467-020-15706-xAPA
Ntalla, I., Weng, L. C., Cartwright, J. H., Hall, A. W., Sveinbjornsson, G., Tucker, N. R., Choi, S. H., Chaffin, M. D., Roselli, C., Barnes, M. R., Mifsud, B., Warren, H. R., Hayward, C., Marten, J., Cranley, J. J., Concas, M. P., Gasparini, P., Boutin, T., Kolcic, I., ... Munroe, P. B. (2020).
Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.
Nature Communications,
11(1), [2542].
https://doi.org/10.1038/s41467-020-15706-xVancouver
Ntalla I, Weng LC, Cartwright JH, Hall AW, Sveinbjornsson G, Tucker NR et al.
Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.
Nature Communications. 2020 Dec 1;11(1). 2542.
https://doi.org/10.1038/s41467-020-15706-xAuthor
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 V. ; 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, David O. ; Gudbjartsson, Daniel F. ; 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. / Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction. In: Nature Communications. 2020 ; Vol. 11, No. 1.
Bibtex
@article{37821af72d9b45fcb4f8c84f859eb48f,
title = "Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction",
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.",
author = "Ioanna Ntalla and Weng, {Lu Chen} and Cartwright, {James H.} and Hall, {Amelia Weber} and Gardar Sveinbjornsson and Tucker, {Nathan R.} and Choi, {Seung Hoan} and Chaffin, {Mark D.} and Carolina Roselli and Barnes, {Michael R.} and Borbala Mifsud and Warren, {Helen R.} and Caroline Hayward and Jonathan Marten and Cranley, {James J.} and Concas, {Maria Pina} and Paolo Gasparini and Thibaud Boutin and Ivana Kolcic and Ozren Polasek and Igor Rudan and Araujo, {Nathalia M.} and Lima-Costa, {Maria Fernanda} and Ribeiro, {Antonio Luiz P.} and Souza, {Renan P.} and Eduardo Tarazona-Santos and Vilmantas Giedraitis and Erik Ingelsson and Anubha Mahajan and Morris, {Andrew P.} and {Del Greco M}, Fabiola and Luisa Foco and Martin G{\"o}gele and Hicks, {Andrew A.} and Cook, {James P.} and Lars Lind and Lindgren, {Cecilia M.} and Johan Sundstr{\"o}m and Nelson, {Christopher P.} and Riaz, {Muhammad B.} and Samani, {Nilesh J.} and Gianfranco Sinagra and Sheila Ulivi and Mika K{\"a}h{\"o}nen and Mishra, {Pashupati P.} and Nina Mononen and Kjell Nikus and Caulfield, {Mark J.} and Anna Dominiczak and Sandosh Padmanabhan and Montasser, {May E.} and O{\textquoteright}Connell, {Jeff R.} and Kathleen Ryan and Shuldiner, {Alan R.} and Stefanie Aeschbacher and David Conen and Lorenz Risch and S{\'e}bastien Th{\'e}riault and Nina Hutri-K{\"a}h{\"o}nen and Terho Lehtim{\"a}ki and Lyytik{\"a}inen, {Leo Pekka} and Raitakari, {Olli T.} and Barnes, {Catriona L.K.} and Harry Campbell and Joshi, {Peter K.} and Wilson, {James F.} and Aaron Isaacs and Kors, {Jan A.} and {van Duijn}, {Cornelia M.} and Huang, {Paul L.} and Vilmundur Gudnason and Harris, {Tamara B.} and Launer, {Lenore J.} and Smith, {Albert V.} and Bottinger, {Erwin P.} and Loos, {Ruth J.F.} and Nadkarni, {Girish N.} and Preuss, {Michael H.} and Adolfo Correa and Hao Mei and James Wilson and Thomas Meitinger and Martina M{\"u}ller-Nurasyid and Annette Peters and Melanie Waldenberger and Massimo Mangino and Spector, {Timothy D.} and Michiel Rienstra and {van de Vegte}, {Yordi J.} and {van der Harst}, Pim and Niek Verweij and Stefan K{\"a}{\"a}b and Katharina Schramm and Sinner, {Moritz F.} and Konstantin Strauch and Cutler, {Michael J.} and Diane Fatkin and Barry London and Morten Olesen and Roden, {Dan M.} and {Benjamin Shoemaker}, M. and {Gustav Smith}, J. and Biggs, {Mary L.} and Bis, {Joshua C.} and Brody, {Jennifer A.} and Psaty, {Bruce M.} and Kenneth Rice and Nona Sotoodehnia and {De Grandi}, Alessandro and Christian Fuchsberger and Cristian Pattaro and Pramstaller, {Peter P.} and Ian Ford and {Wouter Jukema}, J. and Macfarlane, {Peter W.} and Stella Trompet and Marcus D{\"o}rr and Felix, {Stephan B.} and Uwe V{\"o}lker and Stefan Weiss and Havulinna, {Aki S.} and Antti Jula and Katri S{\"a}{\"a}ksj{\"a}rvi and Veikko Salomaa and Xiuqing Guo and Heckbert, {Susan R.} and Lin, {Henry J.} and Rotter, {Jerome I.} and Taylor, {Kent D.} and Jie Yao and {de Mutsert}, Ren{\'e}e and Maan, {Arie C.} and Mook-Kanamori, {Dennis O.} and Raymond Noordam and Francesco Cucca and Jun Ding and Lakatta, {Edward G.} and Yong Qian and Tarasov, {Kirill V.} and Daniel Levy and Honghuang Lin and Newton-Cheh, {Christopher H.} and Lunetta, {Kathryn L.} and Murray, {Alison D.} and Porteous, {David J.} and Smith, {Blair H.} and Stricker, {Bruno H.} and Andr{\'e} Uitterlinden and {van den Berg}, {Marten E.} and Jeffrey Haessler and Jackson, {Rebecca D.} and Charles Kooperberg and Ulrike Peters and Reiner, {Alexander P.} and Whitsel, {Eric A.} and Alvaro Alonso and Arking, {Dan E.} and Eric Boerwinkle and Ehret, {Georg B.} and Soliman, {Elsayed Z.} and Avery, {Christy L.} and Gogarten, {Stephanie M.} and Kerr, {Kathleen F.} and Laurie, {Cathy C.} and Seyerle, {Amanda A.} and Adrienne Stilp and Solmaz Assa and {Abdullah Said}, M. and {Yldau van der Ende}, M. and Lambiase, {Pier D.} and Michele Orini and Julia Ramirez and {Van Duijvenboden}, Stefan and Arnar, {David O.} and Gudbjartsson, {Daniel F.} and Hilma Holm and Patrick Sulem and Gudmar Thorleifsson and Thorolfsdottir, {Rosa B.} and Unnur Thorsteinsdottir and Benjamin, {Emelia J.} and Andrew Tinker and Kari Stefansson and Ellinor, {Patrick T.} and Yalda Jamshidi and Lubitz, {Steven A.} and Munroe, {Patricia B.}",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-020-15706-x",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",
}
RIS
TY - JOUR
T1 - Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
AU - Ntalla, Ioanna
AU - Weng, Lu Chen
AU - Cartwright, James H.
AU - Hall, Amelia Weber
AU - Sveinbjornsson, Gardar
AU - Tucker, Nathan R.
AU - Choi, Seung Hoan
AU - Chaffin, Mark D.
AU - Roselli, Carolina
AU - Barnes, Michael R.
AU - Mifsud, Borbala
AU - Warren, Helen R.
AU - Hayward, Caroline
AU - Marten, Jonathan
AU - Cranley, James J.
AU - Concas, Maria Pina
AU - Gasparini, Paolo
AU - Boutin, Thibaud
AU - Kolcic, Ivana
AU - Polasek, Ozren
AU - Rudan, Igor
AU - Araujo, Nathalia M.
AU - Lima-Costa, Maria Fernanda
AU - Ribeiro, Antonio Luiz P.
AU - Souza, Renan P.
AU - Tarazona-Santos, Eduardo
AU - Giedraitis, Vilmantas
AU - Ingelsson, Erik
AU - Mahajan, Anubha
AU - Morris, Andrew P.
AU - Del Greco M, Fabiola
AU - Foco, Luisa
AU - Gögele, Martin
AU - Hicks, Andrew A.
AU - Cook, James P.
AU - Lind, Lars
AU - Lindgren, Cecilia M.
AU - Sundström, Johan
AU - Nelson, Christopher P.
AU - Riaz, Muhammad B.
AU - Samani, Nilesh J.
AU - Sinagra, Gianfranco
AU - Ulivi, Sheila
AU - Kähönen, Mika
AU - Mishra, Pashupati P.
AU - Mononen, Nina
AU - Nikus, Kjell
AU - Caulfield, Mark J.
AU - Dominiczak, Anna
AU - Padmanabhan, Sandosh
AU - Montasser, May E.
AU - O’Connell, Jeff R.
AU - Ryan, Kathleen
AU - Shuldiner, Alan R.
AU - Aeschbacher, Stefanie
AU - Conen, David
AU - Risch, Lorenz
AU - Thériault, Sébastien
AU - Hutri-Kähönen, Nina
AU - Lehtimäki, Terho
AU - Lyytikäinen, Leo Pekka
AU - Raitakari, Olli T.
AU - Barnes, Catriona L.K.
AU - Campbell, Harry
AU - Joshi, Peter K.
AU - Wilson, James F.
AU - Isaacs, Aaron
AU - Kors, Jan A.
AU - van Duijn, Cornelia M.
AU - Huang, Paul L.
AU - Gudnason, Vilmundur
AU - Harris, Tamara B.
AU - Launer, Lenore J.
AU - Smith, Albert V.
AU - Bottinger, Erwin P.
AU - Loos, Ruth J.F.
AU - Nadkarni, Girish N.
AU - Preuss, Michael H.
AU - Correa, Adolfo
AU - Mei, Hao
AU - Wilson, James
AU - Meitinger, Thomas
AU - Müller-Nurasyid, Martina
AU - Peters, Annette
AU - Waldenberger, Melanie
AU - Mangino, Massimo
AU - Spector, Timothy D.
AU - Rienstra, Michiel
AU - van de Vegte, Yordi J.
AU - van der Harst, Pim
AU - Verweij, Niek
AU - Kääb, Stefan
AU - Schramm, Katharina
AU - Sinner, Moritz F.
AU - Strauch, Konstantin
AU - Cutler, Michael J.
AU - Fatkin, Diane
AU - London, Barry
AU - Olesen, Morten
AU - Roden, Dan M.
AU - Benjamin Shoemaker, M.
AU - Gustav Smith, J.
AU - Biggs, Mary L.
AU - Bis, Joshua C.
AU - Brody, Jennifer A.
AU - Psaty, Bruce M.
AU - Rice, Kenneth
AU - Sotoodehnia, Nona
AU - De Grandi, Alessandro
AU - Fuchsberger, Christian
AU - Pattaro, Cristian
AU - Pramstaller, Peter P.
AU - Ford, Ian
AU - Wouter Jukema, J.
AU - Macfarlane, Peter W.
AU - Trompet, Stella
AU - Dörr, Marcus
AU - Felix, Stephan B.
AU - Völker, Uwe
AU - Weiss, Stefan
AU - Havulinna, Aki S.
AU - Jula, Antti
AU - Sääksjärvi, Katri
AU - Salomaa, Veikko
AU - Guo, Xiuqing
AU - Heckbert, Susan R.
AU - Lin, Henry J.
AU - Rotter, Jerome I.
AU - Taylor, Kent D.
AU - Yao, Jie
AU - de Mutsert, Renée
AU - Maan, Arie C.
AU - Mook-Kanamori, Dennis O.
AU - Noordam, Raymond
AU - Cucca, Francesco
AU - Ding, Jun
AU - Lakatta, Edward G.
AU - Qian, Yong
AU - Tarasov, Kirill V.
AU - Levy, Daniel
AU - Lin, Honghuang
AU - Newton-Cheh, Christopher H.
AU - Lunetta, Kathryn L.
AU - Murray, Alison D.
AU - Porteous, David J.
AU - Smith, Blair H.
AU - Stricker, Bruno H.
AU - Uitterlinden, André
AU - van den Berg, Marten E.
AU - Haessler, Jeffrey
AU - Jackson, Rebecca D.
AU - Kooperberg, Charles
AU - Peters, Ulrike
AU - Reiner, Alexander P.
AU - Whitsel, Eric A.
AU - Alonso, Alvaro
AU - Arking, Dan E.
AU - Boerwinkle, Eric
AU - Ehret, Georg B.
AU - Soliman, Elsayed Z.
AU - Avery, Christy L.
AU - Gogarten, Stephanie M.
AU - Kerr, Kathleen F.
AU - Laurie, Cathy C.
AU - Seyerle, Amanda A.
AU - Stilp, Adrienne
AU - Assa, Solmaz
AU - Abdullah Said, M.
AU - Yldau van der Ende, M.
AU - Lambiase, Pier D.
AU - Orini, Michele
AU - Ramirez, Julia
AU - Van Duijvenboden, Stefan
AU - Arnar, David O.
AU - Gudbjartsson, Daniel F.
AU - Holm, Hilma
AU - Sulem, Patrick
AU - Thorleifsson, Gudmar
AU - Thorolfsdottir, Rosa B.
AU - Thorsteinsdottir, Unnur
AU - Benjamin, Emelia J.
AU - Tinker, Andrew
AU - Stefansson, Kari
AU - Ellinor, Patrick T.
AU - Jamshidi, Yalda
AU - Lubitz, Steven A.
AU - Munroe, Patricia B.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85085157192&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-15706-x
DO - 10.1038/s41467-020-15706-x
M3 - Journal article
C2 - 32439900
AN - SCOPUS:85085157192
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2542
ER -
