Publication

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

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., Polasek, O., Rudan, I., Araujo, N. M., Lima-Costa, M. F., Ribeiro, A. L. P., Souza, R. P., Tarazona-Santos, E., Giedraitis, V., Ingelsson, E., Mahajan, A., Morris, A. P., Del Greco M, F., Foco, L., Gögele, M., Hicks, A. A., Cook, J. P., Lind, L., Lindgren, C. M., Sundström, J., Nelson, C. P., Riaz, M. B., Samani, N. J., Sinagra, G., Ulivi, S., Kähönen, M., Mishra, P. P., Mononen, N., Nikus, K., Caulfield, M. J., Dominiczak, A., Padmanabhan, S., Montasser, M. E., O'Connell, J. R., Ryan, K., Shuldiner, A. R., Aeschbacher, S., Conen, D., Risch, L., Thériault, S., Hutri-Kähönen, N., Lehtimäki, T., Lyytikäinen, L-P., Raitakari, O. T., Barnes, C. L. K., Campbell, H., Joshi, P. K., Wilson, J. F., Isaacs, A., Kors, J. A., van Duijn, C. M., Huang, P. L., Gudnason, V., Harris, T. B., Launer, L. J., Smith, A. V., Bottinger, E. P., Loos, R. J. F., Nadkarni, G. N., Preuss, M. H., Correa, A., Mei, H., Wilson, J., Meitinger, T., Müller-Nurasyid, M., Peters, A., Waldenberger, M., Mangino, M., Spector, T. D., Rienstra, M., van de Vegte, Y. J., van der Harst, P., Verweij, N., Kääb, S., Schramm, K., Sinner, M. F., Strauch, K., Cutler, M. J., Fatkin, D., London, B., Olesen, M., Roden, D. M., Benjamin Shoemaker, M., Gustav Smith, J., Biggs, M. L., Bis, J. C., Brody, J. A., Psaty, B. M., Rice, K., Sotoodehnia, N., De Grandi, A., Fuchsberger, C., Pattaro, C., Pramstaller, P. P., Ford, I., Wouter Jukema, J., Macfarlane, P. W., Trompet, S., Dörr, M., Felix, S. B., Völker, U., Weiss, S., Havulinna, A. S., Jula, A., Sääksjärvi, K., Salomaa, V., Guo, X., Heckbert, S. R., Lin, H. J., Rotter, J. I., Taylor, K. D., Yao, J., de Mutsert, R., Maan, A. C., Mook-Kanamori, D. O., Noordam, R., Cucca, F., Ding, J., Lakatta, E. G., Qian, Y., Tarasov, K. V., Levy, D., Lin, H., Newton-Cheh, C. H., Lunetta, K. L., Murray, A. D., Porteous, D. J., Smith, B. H., Stricker, B. H., Uitterlinden, A., van den Berg, M. E., Haessler, J., Jackson, R. D., Kooperberg, C., Peters, U., Reiner, A. P., Whitsel, E. A., Alonso, A., Arking, D. E., Boerwinkle, E., Ehret, G. B., Soliman, E. Z., Avery, C. L., Gogarten, S. M., Kerr, K. F., Laurie, C. C., Seyerle, A. A., Stilp, A., Assa, S., Abdullah Said, M., Yldau van der Ende, M., Lambiase, P. D., Orini, M., Ramirez, J., Van Duijvenboden, S., Arnar, D. O., Gudbjartsson, D. F., Holm, H., Sulem, P., Thorleifsson, G., Thorolfsdottir, R. B., Thorsteinsdottir, U., Benjamin, E. J., Tinker, A., Stefansson, K., Ellinor, P. T., Jamshidi, Y., Lubitz, S. A. & Munroe, P. B., 21-May-2020, In : Nature Communications. 11, 1, 12 p., 2542.

Research output: Contribution to journalArticleAcademicpeer-review

APA

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-x

Author

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.

Harvard

Ntalla, I, Weng, L-C, 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, L-P, 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-x

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, 21.05.2020.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Ntalla I, Weng L-C, 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 May 21;11(1). 2542. https://doi.org/10.1038/s41467-020-15706-x


BibTeX

@article{2ff3fb3efa6e44cc85f2e63823a00247,
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 Lu-Chen Weng 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'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 Leo-Pekka Lyytik{\"a}inen 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 = may,
day = "21",
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 - 2020/5/21

Y1 - 2020/5/21

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.

U2 - 10.1038/s41467-020-15706-x

DO - 10.1038/s41467-020-15706-x

M3 - Article

C2 - 32439900

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2542

ER -

ID: 125776332