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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
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 i...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2020
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242331/ https://www.ncbi.nlm.nih.gov/pubmed/32439900 http://dx.doi.org/10.1038/s41467-020-15706-x |
| _version_ | 1783537216730955776 |
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| 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. |
| author_facet | 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. |
| author_sort | Ntalla, Ioanna |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-7242331 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-72423312020-05-29 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. Nat Commun Article 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. Nature Publishing Group UK 2020-05-21 /pmc/articles/PMC7242331/ /pubmed/32439900 http://dx.doi.org/10.1038/s41467-020-15706-x Text en © The Author(s) 2020 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/. |
| spellingShingle | Article 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 |
| title | Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction |
| title_full | Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction |
| title_fullStr | Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction |
| title_full_unstemmed | Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction |
| title_short | Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction |
| title_sort | multi-ancestry gwas of the electrocardiographic pr interval identifies 202 loci underlying cardiac conduction |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242331/ https://www.ncbi.nlm.nih.gov/pubmed/32439900 http://dx.doi.org/10.1038/s41467-020-15706-x |
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