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Genetic loci associated with heart rate variability and their effects on cardiac disease risk
Authors :
Nolte, Ilja M. Munoz, M. Loretto Tragante, Vinicius Amare, Azmeraw T. Jansen, Rick Vaez, Ahmad von der Heyde, Benedikt Avery, Christy L. Bis, Joshua C. Dierckx, Bram van Dongen, Jenny Gogarten, Stephanie M. Goyette, Philippe Hernesniemi, Jussi Huikari, Ville Hwang, Shih-Jen Jaju, Deepali Kerr, Kathleen F. Kluttig, Alexander Krijthe, Bouwe P. Kumar, Jitender van der Laan, Sander W. Lyytikainen, Leo-Pekka Maihofer, Adam X. Minassian, Arpi van der Most, Peter J. Mueller-Nurasyid, Martina Nivard, Michel Salvi, Erika Stewart, James D. Thayer, Julian F. Verweij, Niek Wong, Andrew Zabaneh, Delilah Zafarmand, Mohammad H. Abdellaoui, Abdel Albarwani, Sulayma Albert, Christine Alonso, Alvaro Ashar, Foram Auvinen, Juha Axelsson, Tomas Baker, Dewleen G. de Bakker, Paul I. W. Barcella, Matteo Bayoumi, Riad Bieringa, Rob J. Boomsma, Dorret Boucher, Gabrielle Britton, Annie R. Christophersen, Ingrid E. Dietrich, Andrea Ehret, George B. Ellinor, Patrick T. Eskola, Markku Felix, Janine F. Floras, John S. Franco, Oscar H. Friberg, Peter Gademan, Maaike G. J. Geyer, Mark A. Giedraitis, Vilmantas Hartman, Catharina A. Hemerich, Daiane Hofman, Albert Hottenga, Jouke-Jan Huikuri, Heikki Hutri-Kahonen, Nina Jouven, Xavier Junttila, Juhani Juonala, Markus Kiviniemi, Antti M. Kors, Jan A. Kumari, Meena Kuznetsova, Tatiana Laurie, Cathy C. Lefrandt, Joop D. Li, Yong Li, Yun Liao, Duanping Limacher, Marian C. Lin, Henry J. Lindgren, Cecilia M. Lubitz, Steven A. Mahajan, Anubha McKnight, Barbara zu Schwabedissen, Henriette Meyer Milaneschi, Yuri Mononen, Nina Morris, Andrew P. Nalls, Mike A. Navis, Gerjan Neijts, Melanie Nikus, Kjell North, Kari E. O'Connor, Daniel T. Ormel, Johan Perz, Siegfried Peters, Annette Psaty, Bruce M. Raitakari, Olli T. Risbrough, Victoria B. Sinner, Moritz F. Siscovick, David Smit, Johannes H. Smith, Nicholas L. Soliman, Elsayed Z. Sotoodehnia, Nona Staessen, Jan A. Stein, Phyllis K. Stilp, Adrienne M. Stolarz-Skrzypek, Katarzyna Strauch, Konstantin Sundstrom, Johan Swenne, Cees A. Syvänen, Ann-Christine Tardif, Jean-Claude Taylor, Kent D. Teumer, Alexander Thornton, Timothy A. Tinker, Lesley E. Uitterlinden, Andre G. van Setten, Jessica Voss, Andreas Waldenberger, Melanie Wilhelmsen, Kirk C. Willemsen, Gonneke Wong, Quenna Zhang, Zhu-Ming Zonderman, Alan B. Cusi, Daniele Evans, Michele K. Greiser, Halina K. van der Harst, Pim Hassan, Mohammad Ingelsson, Erik Jarvelin, Marjo-Riitta Kaab, Stefan Kahonen, Mika Kivimaki, Mika Kooperberg, Charles Kuh, Diana Lehtimaki, Terho Lind, Lars Nievergelt, Caroline M. O'Donnell, Chris J. Oldehinkel, Albertine J. Penninx, Brenda Reiner, Alexander P. Riese, Harriette van Roon, Arie M. Rioux, John D. Rotter, Jerome I. Sofer, Tamar Stricker, Bruno H. Tiemeier, Henning Vrijkotte, Tanja G. M. Asselbergs, Folkert W. Brundel, Bianca J. J. M. Heckbert, Susan R. Whitsel, Eric A. den Hoed, Marcel Snieder, Harold de Geus, Eco J. C. Nolte, Ilja M. Munoz, M. Loretto Tragante, Vinicius Amare, Azmeraw T. Jansen, Rick Vaez, Ahmad von der Heyde, Benedikt Avery, Christy L. Bis, Joshua C. Dierckx, Bram van Dongen, Jenny Gogarten, Stephanie M. Goyette, Philippe Hernesniemi, Jussi Huikari, Ville Hwang, Shih-Jen Jaju, Deepali Kerr, Kathleen F. Kluttig, Alexander Krijthe, Bouwe P. Kumar, Jitender van der Laan, Sander W. Lyytikainen, Leo-Pekka Maihofer, Adam X. Minassian, Arpi van der Most, Peter J. Mueller-Nurasyid, Martina Nivard, Michel Salvi, Erika Stewart, James D. Thayer, Julian F. Verweij, Niek Wong, Andrew Zabaneh, Delilah Zafarmand, Mohammad H. Abdellaoui, Abdel Albarwani, Sulayma Albert, Christine Alonso, Alvaro Ashar, Foram Auvinen, Juha Axelsson, Tomas Baker, Dewleen G. de Bakker, Paul I. W. Barcella, Matteo Bayoumi, Riad Bieringa, Rob J. Boomsma, Dorret Boucher, Gabrielle Britton, Annie R. Christophersen, Ingrid E. Dietrich, Andrea Ehret, George B. Ellinor, Patrick T. Eskola, Markku Felix, Janine F. Floras, John S. Franco, Oscar H. Friberg, Peter Gademan, Maaike G. J. Geyer, Mark A. Giedraitis, Vilmantas Hartman, Catharina A. Hemerich, Daiane Hofman, Albert Hottenga, Jouke-Jan Huikuri, Heikki Hutri-Kahonen, Nina Jouven, Xavier Junttila, Juhani Juonala, Markus Kiviniemi, Antti M. Kors, Jan A. Kumari, Meena Kuznetsova, Tatiana Laurie, Cathy C. Lefrandt, Joop D. Li, Yong Li, Yun Liao, Duanping Limacher, Marian C. Lin, Henry J. Lindgren, Cecilia M. Lubitz, Steven A. Mahajan, Anubha McKnight, Barbara zu Schwabedissen, Henriette Meyer Milaneschi, Yuri Mononen, Nina Morris, Andrew P. Nalls, Mike A. Navis, Gerjan Neijts, Melanie Nikus, Kjell North, Kari E. O'Connor, Daniel T. Ormel, Johan Perz, Siegfried Peters, Annette Psaty, Bruce M. Raitakari, Olli T. Risbrough, Victoria B. Sinner, Moritz F. Siscovick, David Smit, Johannes H. Smith, Nicholas L. Soliman, Elsayed Z. Sotoodehnia, Nona Staessen, Jan A. Stein, Phyllis K. Stilp, Adrienne M. Stolarz-Skrzypek, Katarzyna Strauch, Konstantin Sundstrom, Johan Swenne, Cees A. Syvänen, Ann-Christine Tardif, Jean-Claude Taylor, Kent D. Teumer, Alexander Thornton, Timothy A. Tinker, Lesley E. Uitterlinden, Andre G. van Setten, Jessica Voss, Andreas Waldenberger, Melanie Wilhelmsen, Kirk C. Willemsen, Gonneke Wong, Quenna Zhang, Zhu-Ming Zonderman, Alan B. Cusi, Daniele Evans, Michele K. Greiser, Halina K. van der Harst, Pim Hassan, Mohammad Ingelsson, Erik Jarvelin, Marjo-Riitta Kaab, Stefan Kahonen, Mika Kivimaki, Mika Kooperberg, Charles Kuh, Diana Lehtimaki, Terho Lind, Lars Nievergelt, Caroline M. O'Donnell, Chris J. Oldehinkel, Albertine J. Penninx, Brenda Reiner, Alexander P. Riese, Harriette van Roon, Arie M. Rioux, John D. Rotter, Jerome I. Sofer, Tamar Stricker, Bruno H. Tiemeier, Henning Vrijkotte, Tanja G. M. Asselbergs, Folkert W. Brundel, Bianca J. J. M. Heckbert, Susan R. Whitsel, Eric A. den Hoed, Marcel Snieder, Harold de Geus, Eco J. C.
Publication Year :
2017
Abstract
Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
Details
Database :
OAIster
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1234033535
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1038.ncomms15805