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PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Exami...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2018
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060178/ https://www.ncbi.nlm.nih.gov/pubmed/30046033 http://dx.doi.org/10.1038/s41467-018-04766-9 |
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| author | van Setten, Jessica Brody, Jennifer A. Jamshidi, Yalda Swenson, Brenton R. Butler, Anne M. Campbell, Harry Del Greco, Fabiola M. Evans, Daniel S. Gibson, Quince Gudbjartsson, Daniel F. Kerr, Kathleen F. Krijthe, Bouwe P. Lyytikäinen, Leo-Pekka Müller, Christian Müller-Nurasyid, Martina Nolte, Ilja M. Padmanabhan, Sandosh Ritchie, Marylyn D. Robino, Antonietta Smith, Albert V. Steri, Maristella Tanaka, Toshiko Teumer, Alexander Trompet, Stella Ulivi, Sheila Verweij, Niek Yin, Xiaoyan Arnar, David O. Asselbergs, Folkert W. Bader, Joel S. Barnard, John Bis, Josh Blankenberg, Stefan Boerwinkle, Eric Bradford, Yuki Buckley, Brendan M. Chung, Mina K. Crawford, Dana den Hoed, Marcel Denny, Josh C. Dominiczak, Anna F. Ehret, Georg B. Eijgelsheim, Mark Ellinor, Patrick T. Felix, Stephan B. Franco, Oscar H. Franke, Lude Harris, Tamara B. Holm, Hilma Ilaria, Gandin Iorio, Annamaria Kähönen, Mika Kolcic, Ivana Kors, Jan A. Lakatta, Edward G. Launer, Lenore J. Lin, Honghuang Lin, Henry J. Loos, Ruth J. F. Lubitz, Steven A. Macfarlane, Peter W. Magnani, Jared W. Leach, Irene Mateo Meitinger, Thomas Mitchell, Braxton D. Munzel, Thomas Papanicolaou, George J. Peters, Annette Pfeufer, Arne Pramstaller, Peter P. Raitakari, Olli T. Rotter, Jerome I. Rudan, Igor Samani, Nilesh J. Schlessinger, David Silva Aldana, Claudia T. Sinner, Moritz F. Smith, Jonathan D. Snieder, Harold Soliman, Elsayed Z. Spector, Timothy D. Stott, David J. Strauch, Konstantin Tarasov, Kirill V. Thorsteinsdottir, Unnur Uitterlinden, Andre G. Van Wagoner, David R. Völker, Uwe Völzke, Henry Waldenberger, Melanie Jan Westra, Harm Wild, Philipp S. Zeller, Tanja Alonso, Alvaro Avery, Christy L. Bandinelli, Stefania Benjamin, Emelia J. Cucca, Francesco Dörr, Marcus Ferrucci, Luigi Gasparini, Paolo Gudnason, Vilmundur Hayward, Caroline Heckbert, Susan R. Hicks, Andrew A. Jukema, J. Wouter Kääb, Stefan Lehtimäki, Terho Liu, Yongmei Munroe, Patricia B. Parsa, Afshin Polasek, Ozren Psaty, Bruce M. Roden, Dan M. Schnabel, Renate B. Sinagra, Gianfranco Stefansson, Kari Stricker, Bruno H. van der Harst, Pim van Duijn, Cornelia M. Wilson, James F. Gharib, Sina A. de Bakker, Paul I. W. Isaacs, Aaron Arking, Dan E. Sotoodehnia, Nona |
| author_facet | van Setten, Jessica Brody, Jennifer A. Jamshidi, Yalda Swenson, Brenton R. Butler, Anne M. Campbell, Harry Del Greco, Fabiola M. Evans, Daniel S. Gibson, Quince Gudbjartsson, Daniel F. Kerr, Kathleen F. Krijthe, Bouwe P. Lyytikäinen, Leo-Pekka Müller, Christian Müller-Nurasyid, Martina Nolte, Ilja M. Padmanabhan, Sandosh Ritchie, Marylyn D. Robino, Antonietta Smith, Albert V. Steri, Maristella Tanaka, Toshiko Teumer, Alexander Trompet, Stella Ulivi, Sheila Verweij, Niek Yin, Xiaoyan Arnar, David O. Asselbergs, Folkert W. Bader, Joel S. Barnard, John Bis, Josh Blankenberg, Stefan Boerwinkle, Eric Bradford, Yuki Buckley, Brendan M. Chung, Mina K. Crawford, Dana den Hoed, Marcel Denny, Josh C. Dominiczak, Anna F. Ehret, Georg B. Eijgelsheim, Mark Ellinor, Patrick T. Felix, Stephan B. Franco, Oscar H. Franke, Lude Harris, Tamara B. Holm, Hilma Ilaria, Gandin Iorio, Annamaria Kähönen, Mika Kolcic, Ivana Kors, Jan A. Lakatta, Edward G. Launer, Lenore J. Lin, Honghuang Lin, Henry J. Loos, Ruth J. F. Lubitz, Steven A. Macfarlane, Peter W. Magnani, Jared W. Leach, Irene Mateo Meitinger, Thomas Mitchell, Braxton D. Munzel, Thomas Papanicolaou, George J. Peters, Annette Pfeufer, Arne Pramstaller, Peter P. Raitakari, Olli T. Rotter, Jerome I. Rudan, Igor Samani, Nilesh J. Schlessinger, David Silva Aldana, Claudia T. Sinner, Moritz F. Smith, Jonathan D. Snieder, Harold Soliman, Elsayed Z. Spector, Timothy D. Stott, David J. Strauch, Konstantin Tarasov, Kirill V. Thorsteinsdottir, Unnur Uitterlinden, Andre G. Van Wagoner, David R. Völker, Uwe Völzke, Henry Waldenberger, Melanie Jan Westra, Harm Wild, Philipp S. Zeller, Tanja Alonso, Alvaro Avery, Christy L. Bandinelli, Stefania Benjamin, Emelia J. Cucca, Francesco Dörr, Marcus Ferrucci, Luigi Gasparini, Paolo Gudnason, Vilmundur Hayward, Caroline Heckbert, Susan R. Hicks, Andrew A. Jukema, J. Wouter Kääb, Stefan Lehtimäki, Terho Liu, Yongmei Munroe, Patricia B. Parsa, Afshin Polasek, Ozren Psaty, Bruce M. Roden, Dan M. Schnabel, Renate B. Sinagra, Gianfranco Stefansson, Kari Stricker, Bruno H. van der Harst, Pim van Duijn, Cornelia M. Wilson, James F. Gharib, Sina A. de Bakker, Paul I. W. Isaacs, Aaron Arking, Dan E. Sotoodehnia, Nona |
| author_sort | van Setten, Jessica |
| collection | PubMed |
| description | Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development. |
| format | Online Article Text |
| id | pubmed-6060178 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-60601782018-07-27 PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity van Setten, Jessica Brody, Jennifer A. Jamshidi, Yalda Swenson, Brenton R. Butler, Anne M. Campbell, Harry Del Greco, Fabiola M. Evans, Daniel S. Gibson, Quince Gudbjartsson, Daniel F. Kerr, Kathleen F. Krijthe, Bouwe P. Lyytikäinen, Leo-Pekka Müller, Christian Müller-Nurasyid, Martina Nolte, Ilja M. Padmanabhan, Sandosh Ritchie, Marylyn D. Robino, Antonietta Smith, Albert V. Steri, Maristella Tanaka, Toshiko Teumer, Alexander Trompet, Stella Ulivi, Sheila Verweij, Niek Yin, Xiaoyan Arnar, David O. Asselbergs, Folkert W. Bader, Joel S. Barnard, John Bis, Josh Blankenberg, Stefan Boerwinkle, Eric Bradford, Yuki Buckley, Brendan M. Chung, Mina K. Crawford, Dana den Hoed, Marcel Denny, Josh C. Dominiczak, Anna F. Ehret, Georg B. Eijgelsheim, Mark Ellinor, Patrick T. Felix, Stephan B. Franco, Oscar H. Franke, Lude Harris, Tamara B. Holm, Hilma Ilaria, Gandin Iorio, Annamaria Kähönen, Mika Kolcic, Ivana Kors, Jan A. Lakatta, Edward G. Launer, Lenore J. Lin, Honghuang Lin, Henry J. Loos, Ruth J. F. Lubitz, Steven A. Macfarlane, Peter W. Magnani, Jared W. Leach, Irene Mateo Meitinger, Thomas Mitchell, Braxton D. Munzel, Thomas Papanicolaou, George J. Peters, Annette Pfeufer, Arne Pramstaller, Peter P. Raitakari, Olli T. Rotter, Jerome I. Rudan, Igor Samani, Nilesh J. Schlessinger, David Silva Aldana, Claudia T. Sinner, Moritz F. Smith, Jonathan D. Snieder, Harold Soliman, Elsayed Z. Spector, Timothy D. Stott, David J. Strauch, Konstantin Tarasov, Kirill V. Thorsteinsdottir, Unnur Uitterlinden, Andre G. Van Wagoner, David R. Völker, Uwe Völzke, Henry Waldenberger, Melanie Jan Westra, Harm Wild, Philipp S. Zeller, Tanja Alonso, Alvaro Avery, Christy L. Bandinelli, Stefania Benjamin, Emelia J. Cucca, Francesco Dörr, Marcus Ferrucci, Luigi Gasparini, Paolo Gudnason, Vilmundur Hayward, Caroline Heckbert, Susan R. Hicks, Andrew A. Jukema, J. Wouter Kääb, Stefan Lehtimäki, Terho Liu, Yongmei Munroe, Patricia B. Parsa, Afshin Polasek, Ozren Psaty, Bruce M. Roden, Dan M. Schnabel, Renate B. Sinagra, Gianfranco Stefansson, Kari Stricker, Bruno H. van der Harst, Pim van Duijn, Cornelia M. Wilson, James F. Gharib, Sina A. de Bakker, Paul I. W. Isaacs, Aaron Arking, Dan E. Sotoodehnia, Nona Nat Commun Article Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development. Nature Publishing Group UK 2018-07-25 /pmc/articles/PMC6060178/ /pubmed/30046033 http://dx.doi.org/10.1038/s41467-018-04766-9 Text en © The Author(s) 2018 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 van Setten, Jessica Brody, Jennifer A. Jamshidi, Yalda Swenson, Brenton R. Butler, Anne M. Campbell, Harry Del Greco, Fabiola M. Evans, Daniel S. Gibson, Quince Gudbjartsson, Daniel F. Kerr, Kathleen F. Krijthe, Bouwe P. Lyytikäinen, Leo-Pekka Müller, Christian Müller-Nurasyid, Martina Nolte, Ilja M. Padmanabhan, Sandosh Ritchie, Marylyn D. Robino, Antonietta Smith, Albert V. Steri, Maristella Tanaka, Toshiko Teumer, Alexander Trompet, Stella Ulivi, Sheila Verweij, Niek Yin, Xiaoyan Arnar, David O. Asselbergs, Folkert W. Bader, Joel S. Barnard, John Bis, Josh Blankenberg, Stefan Boerwinkle, Eric Bradford, Yuki Buckley, Brendan M. Chung, Mina K. Crawford, Dana den Hoed, Marcel Denny, Josh C. Dominiczak, Anna F. Ehret, Georg B. Eijgelsheim, Mark Ellinor, Patrick T. Felix, Stephan B. Franco, Oscar H. Franke, Lude Harris, Tamara B. Holm, Hilma Ilaria, Gandin Iorio, Annamaria Kähönen, Mika Kolcic, Ivana Kors, Jan A. Lakatta, Edward G. Launer, Lenore J. Lin, Honghuang Lin, Henry J. Loos, Ruth J. F. Lubitz, Steven A. Macfarlane, Peter W. Magnani, Jared W. Leach, Irene Mateo Meitinger, Thomas Mitchell, Braxton D. Munzel, Thomas Papanicolaou, George J. Peters, Annette Pfeufer, Arne Pramstaller, Peter P. Raitakari, Olli T. Rotter, Jerome I. Rudan, Igor Samani, Nilesh J. Schlessinger, David Silva Aldana, Claudia T. Sinner, Moritz F. Smith, Jonathan D. Snieder, Harold Soliman, Elsayed Z. Spector, Timothy D. Stott, David J. Strauch, Konstantin Tarasov, Kirill V. Thorsteinsdottir, Unnur Uitterlinden, Andre G. Van Wagoner, David R. Völker, Uwe Völzke, Henry Waldenberger, Melanie Jan Westra, Harm Wild, Philipp S. Zeller, Tanja Alonso, Alvaro Avery, Christy L. Bandinelli, Stefania Benjamin, Emelia J. Cucca, Francesco Dörr, Marcus Ferrucci, Luigi Gasparini, Paolo Gudnason, Vilmundur Hayward, Caroline Heckbert, Susan R. Hicks, Andrew A. Jukema, J. Wouter Kääb, Stefan Lehtimäki, Terho Liu, Yongmei Munroe, Patricia B. Parsa, Afshin Polasek, Ozren Psaty, Bruce M. Roden, Dan M. Schnabel, Renate B. Sinagra, Gianfranco Stefansson, Kari Stricker, Bruno H. van der Harst, Pim van Duijn, Cornelia M. Wilson, James F. Gharib, Sina A. de Bakker, Paul I. W. Isaacs, Aaron Arking, Dan E. Sotoodehnia, Nona PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity |
| title | PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity |
| title_full | PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity |
| title_fullStr | PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity |
| title_full_unstemmed | PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity |
| title_short | PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity |
| title_sort | pr interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060178/ https://www.ncbi.nlm.nih.gov/pubmed/30046033 http://dx.doi.org/10.1038/s41467-018-04766-9 |
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