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1. Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author

Ilja M. Nolte, M. Loretto Munoz, Vinicius Tragante, Azmeraw T. Amare, Rick Jansen, Ahmad Vaez, Benedikt von der Heyde, Christy L. Avery, Joshua C. Bis, Bram Dierckx, Jenny van Dongen, Stephanie M. Gogarten, Philippe Goyette, Jussi Hernesniemi, Ville Huikari, Shih-Jen Hwang, Deepali Jaju, Kathleen F. Kerr, Alexander Kluttig, Bouwe P. Krijthe, Jitender Kumar, Sander W. van der Laan, Leo-Pekka Lyytikäinen, Adam X. Maihofer, Arpi Minassian, Peter J. van der Most, Martina Müller-Nurasyid, Michel Nivard, Erika Salvi, James D. Stewart, Julian F. Thayer, Niek Verweij, Andrew Wong, Delilah Zabaneh, Mohammad H. Zafarmand, Abdel Abdellaoui, Sulayma Albarwani, Christine Albert, Alvaro Alonso, Foram Ashar, Juha Auvinen, Tomas Axelsson, Dewleen G. Baker, Paul I. W. de Bakker, Matteo Barcella, Riad Bayoumi, Rob J. Bieringa, Dorret Boomsma, Gabrielle Boucher, Annie R. Britton, Ingrid Christophersen, Andrea Dietrich, George B. Ehret, Patrick T. Ellinor, Markku Eskola, Janine F. Felix, John S. Floras, Oscar H. Franco, Peter Friberg, Maaike G. J. Gademan, Mark A. Geyer, Vilmantas Giedraitis, Catharina A. Hartman, Daiane Hemerich, Albert Hofman, Jouke-Jan Hottenga, Heikki Huikuri, Nina Hutri-Kähönen, Xavier Jouven, Juhani Junttila, Markus Juonala, Antti M. Kiviniemi, Jan A. Kors, Meena Kumari, Tatiana Kuznetsova, Cathy C. Laurie, Joop D. Lefrandt, Yong Li, Yun Li, Duanping Liao, Marian C. Limacher, Henry J. Lin, Cecilia M. Lindgren, Steven A. Lubitz, Anubha Mahajan, Barbara McKnight, Henriette Meyer zu Schwabedissen, Yuri Milaneschi, Nina Mononen, Andrew P. Morris, Mike A. Nalls, Gerjan Navis, Melanie Neijts, Kjell Nikus, Kari E. North, Daniel T. O'Connor, Johan Ormel, Siegfried Perz, Annette Peters, Bruce M. Psaty, Olli T. Raitakari, Victoria B. Risbrough, Moritz F. Sinner, David Siscovick, Johannes H. Smit, Nicholas L. Smith, Elsayed Z. Soliman, Nona Sotoodehnia, Jan A. Staessen, Phyllis K. Stein, Adrienne M. Stilp, Katarzyna Stolarz-Skrzypek, Konstantin Strauch, Johan Sundström, Cees A. Swenne, Ann-Christine Syvänen, Jean-Claude Tardif, Kent D. Taylor, Alexander Teumer, Timothy A. Thornton, Lesley E. Tinker, André G. Uitterlinden, Jessica van Setten, Andreas Voss, Melanie Waldenberger, Kirk C. Wilhelmsen, Gonneke Willemsen, Quenna Wong, Zhu-Ming Zhang, Alan B. Zonderman, Daniele Cusi, Michele K. Evans, Halina K. Greiser, Pim van der Harst, Mohammad Hassan, Erik Ingelsson, Marjo-Riitta Järvelin, Stefan Kääb, Mika Kähönen, Mika Kivimaki, Charles Kooperberg, Diana Kuh, Terho Lehtimäki, Lars Lind, Caroline M. Nievergelt, Chris J. O'Donnell, Albertine J. Oldehinkel, Brenda Penninx, Alexander P. Reiner, Harriëtte Riese, Arie M. van Roon, John D. Rioux, Jerome I. Rotter, Tamar Sofer, Bruno H. Stricker, Henning Tiemeier, Tanja G. M. Vrijkotte, Folkert W. Asselbergs, Bianca J. J. M. Brundel, Susan R. Heckbert, Eric A. Whitsel, Marcel den Hoed, Harold Snieder, and Eco J. C. de Geus

Subjects
Science
Abstract

Heart rate variability (HRV) describes the individual variation in cardiac cycle duration and is a measure of vagal control of heart rate. Here, the authors identify seventeen single-nucleotide polymorphisms associated with HRV, lending new insight into the vagal regulation of heart rhythm.

Published
2017
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2. Erratum: Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author

Ilja M. Nolte, M. Loretto Munoz, Vinicius Tragante, Azmeraw T. Amare, Rick Jansen, Ahmad Vaez, Benedikt von der Heyde, Christy L. Avery, Joshua C. Bis, Bram Dierckx, Jenny van Dongen, Stephanie M. Gogarten, Philippe Goyette, Jussi Hernesniemi, Ville Huikari, Shih-Jen Hwang, Deepali Jaju, Kathleen F. Kerr, Alexander Kluttig, Bouwe P. Krijthe, Jitender Kumar, Sander W. van der Laan, Leo-Pekka Lyytikäinen, Adam X. Maihofer, Arpi Minassian, Peter J. van der Most, Martina Müller-Nurasyid, Michel Nivard, Erika Salvi, James D. Stewart, Julian F. Thayer, Niek Verweij, Andrew Wong, Delilah Zabaneh, Mohammad H. Zafarmand, Abdel Abdellaoui, Sulayma Albarwani, Christine Albert, Alvaro Alonso, Foram Ashar, Juha Auvinen, Tomas Axelsson, Dewleen G. Baker, Paul I. W. de Bakker, Matteo Barcella, Riad Bayoumi, Rob J. Bieringa, Dorret Boomsma, Gabrielle Boucher, Annie R. Britton, Ingrid Christophersen, Andrea Dietrich, George B. Ehret, Patrick T. Ellinor, Markku Eskola, Janine F. Felix, John S. Floras, Oscar H. Franco, Peter Friberg, Maaike G. J. Gademan, Mark A. Geyer, Vilmantas Giedraitis, Catharina A. Hartman, Daiane Hemerich, Albert Hofman, Jouke-Jan Hottenga, Heikki Huikuri, Nina Hutri-Kähönen, Xavier Jouven, Juhani Junttila, Markus Juonala, Antti M. Kiviniemi, Jan A. Kors, Meena Kumari, Tatiana Kuznetsova, Cathy C. Laurie, Joop D. Lefrandt, Yong Li, Yun Li, Duanping Liao, Marian C. Limacher, Henry J. Lin, Cecilia M. Lindgren, Steven A. Lubitz, Anubha Mahajan, Barbara McKnight, Henriette Meyer zu Schwabedissen, Yuri Milaneschi, Nina Mononen, Andrew P. Morris, Mike A. Nalls, Gerjan Navis, Melanie Neijts, Kjell Nikus, Kari E. North, Daniel T. O'Connor, Johan Ormel, Siegfried Perz, Annette Peters, Bruce M. Psaty, Olli T. Raitakari, Victoria B. Risbrough, Moritz F. Sinner, David Siscovick, Johannes H. Smit, Nicholas L. Smith, Elsayed Z. Soliman, Nona Sotoodehnia, Jan A. Staessen, Phyllis K. Stein, Adrienne M. Stilp, Katarzyna Stolarz-Skrzypek, Konstantin Strauch, Johan Sundström, Cees A. Swenne, Ann-Christine Syvänen, Jean-Claude Tardif, Kent D. Taylor, Alexander Teumer, Timothy A. Thornton, Lesley E. Tinker, André G. Uitterlinden, Jessica van Setten, Andreas Voss, Melanie Waldenberger, Kirk C. Wilhelmsen, Gonneke Willemsen, Quenna Wong, Zhu-Ming Zhang, Alan B Zonderman, Daniele Cusi, Michele K. Evans, Halina K. Greiser, Pim van der Harst, Mohammad Hassan, Erik Ingelsson, Marjo-Riitta Järvelin, Stefan Kääb, Mika Kähönen, Mika Kivimaki, Charles Kooperberg, Diana Kuh, Terho Lehtimäki, Lars Lind, Caroline M. Nievergelt, Chris J. O'Donnell, Albertine J. Oldehinkel, Brenda Penninx, Alexander P. Reiner, Harriëtte Riese, Arie M. van Roon, John D. Rioux, Jerome I. Rotter, Tamar Sofer, Bruno H. Stricker, Henning Tiemeier, Tanja G. M. Vrijkotte, Folkert W. Asselbergs, Bianca J. J.M Brundel, Susan R. Heckbert, Eric A. Whitsel, Marcel den Hoed, Harold Snieder, and Eco J. C. de Geus

Subjects
Science
Abstract

Nature Communications 8: Article number: 15805 (2017); Published: 14 June 2017; Updated: 2 August 2017 In Supplementary Fig. 10 of this Article, images for panels a and b were inadvertently omitted. The correct version of Supplementary Fig. 10 is provided as Supplementary Information associated withthis Erratum.

Published
2017
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3. Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Author

Gerard Temprano‐Sagrera, Colleen M. Sitlani, William P. Bone, Miguel Martin‐Bornez, Benjamin F. Voight, Alanna C. Morrison, Scott M. Damrauer, Paul S. de Vries, Nicholas L. Smith, Maria Sabater‐Lleal, Abbas Dehghan, Adam S Heath, Alanna C Morrison, Alex P Reiner, Andrew Johnson, Anne Richmond, Annette Peters, Astrid van Hylckama Vlieg, Barbara McKnight, Bruce M Psaty, Caroline Hayward, Cavin Ward‐Caviness, Christopher O’Donnell, Daniel Chasman, David P Strachan, David A Tregouet, Dennis Mook‐Kanamori, Dipender Gill, Florian Thibord, Folkert W Asselbergs, Frank W.G. Leebeek, Frits R Rosendaal, Gail Davies, Georg Homuth, Gerard Temprano, Harry Campbell, Herman A Taylor, Jan Bressler, Jennifer E Huffman, Jerome I Rotter, Jie Yao, James F Wilson, Joshua C Bis, Julie M Hahn, Karl C Desch, Kerri L Wiggins, Laura M Raffield, Lawrence F Bielak, Lisa R Yanek, Marcus E Kleber, Martina Mueller, Maryam Kavousi, Massimo Mangino, Melissa Liu, Michael R Brown, Matthew P Conomos, Min‐A Jhun, Ming‐Huei Chen, Moniek P.M. de Maat, Nathan Pankratz, Nicholas L Smith, Patricia A Peyser, Paul Elliot, Paul S de Vries, Peng Wei, Philipp S Wild, Pierre E Morange, Pim van der Harst, Qiong Yang, Ngoc‐Quynh Le, Riccardo Marioni, Ruifang Li, Scott M Damrauer, Simon R Cox, Stella Trompet, Stephan B Felix, Uwe Völker, Weihong Tang, Wolfgang Koenig, J. Wouter Jukema, Xiuqing Guo, Sara Lindstrom, Lu Wang, Erin N Smith, William Gordon, Mariza de Andrade, Jennifer A Brody, Jack W Pattee, Jeffrey Haessler, Ben M Brumpton, Daniel I Chasman, Pierre Suchon, Constance Turman, Marine Germain, James MacDonald, Sigrid K Braekkan, Sebastian M Armasu, Rabecca D Jackson, Jonas B Nielsen, Franco Giulianini, Marja K Puurunen, Manal Ibrahim, Susan R Heckbert, Theo K Bammler, Kelly A Frazer, Bryan M McCauley, Kent Taylor, James S Pankow, Alexander P Reiner, Maiken E Gabrielsen, Jean‐François Deleuze, Chris J O’Donnell, Jihye Kim, Peter Kraft, John‐Bjarne Hansen, John A Heit, Charles Kooperberg, Kristian Hveem, Paul M Ridker, Pierre‐Emmanuel Morange, Andrew D Johnson, Christopher Kabrhel, David‐Alexandre Trégouët, Rainer Malik, Ganesh Chauhan, Matthew Traylor, Muralidharan Sargurupremraj, Yukinori Okada, Aniket Mishra, Loes Rutten‐Jacobs, Anne‐Katrin Giese, Sander W van der Laan, Solveig Gretarsdottir, Christopher D Anderson, Michael Chong, Hieab HH Adams, Tetsuro Ago, Peter Almgren, Philippe Amouyel, Hakan Ay, Traci M Bartz, Oscar R Benavente, Steve Bevan, Giorgio B Boncoraglio, Robert D Brown, Adam S Butterworth, Caty Carrera, Cara L Carty, Wei‐Min Chen, John W Cole, Adolfo Correa, Ioana Cotlarciuc, Carlos Cruchaga, John Danesh, Paul IW de Bakker, Anita L DeStefano, Marcel den Hoed, Qing Duan, Stefan T Engelter, Guido J Falcone, Rebecca F Gottesman, Raji P Grewal, Vilmundur Gudnason, Stefan Gustafsson, Tamara B Harris, Ahamad Hassan, Aki S Havulinna, Elizabeth G Holliday, George Howard, Fang‐Chi Hsu, Hyacinth I Hyacinth, M Arfan Ikram, Erik Ingelsson, Marguerite R Irvin, Xueqiu Jian, Jordi Jiménez‐Conde, Julie A Johnson, J Wouter Jukema, Masahiro Kanai, Keith L Keene, Brett M Kissela, Dawn O Kleindorfer, Michiaki Kubo, Leslie A Lange, Carl D Langefeld, Claudia Langenberg, Lenore J Launer, Jin‐Moo Lee, Robin Lemmens, Didier Leys, Cathryn M Lewis, Wei‐Yu Lin, Arne G Lindgren, Erik Lorentzen, Patrik K Magnusson, Jane Maguire, Ani Manichaikul, Patrick F McArdle, James F Meschia, Braxton D Mitchell, Thomas H Mosley, Michael A Nalls, Toshiharu Ninomiya, Martin J O’Donnell, Sara L Pulit, Kristiina Rannikmäe, Kathryn M Rexrode, Kenneth Rice, Stephen S Rich, Natalia S Rost, Peter M Rothwell, Tatjana Rundek, Ralph L Sacco, Saori Sakaue, Michele M Sale, Veikko Salomaa, Bishwa R Sapkota, Reinhold Schmidt, Carsten O Schmidt, Ulf Schminke, Pankaj Sharma, Agnieszka Slowik, Cathie LM Sudlow, Christian Tanislav, Turgut Tatlisumak, Kent D Taylor, Vincent NS Thijs, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Steffen Tiedt, Christophe Tzourio, Cornelia M van Duijn, Matthew Walters, Nicholas J Wareham, Sylvia Wassertheil‐Smoller, James G Wilson, Salim Yusuf, Najaf Amin, Hugo S Aparicio, Donna K Arnett, John Attia, Alexa S Beiser, Claudine Berr, Julie E Buring, Mariana Bustamante, Valeria Caso, Yu‐Ching Cheng, Seung Hoan Choi, Ayesha Chowhan, Natalia Cullell, Jean‐François Dartigues, Hossein Delavaran, Pilar Delgado, Marcus Dörr, Gunnar Engström, Ian Ford, Wander S Gurpreet, Anders Hamsten, Laura Heitsch, Atsushi Hozawa, Laura Ibanez, Andreea Ilinca, Martin Ingelsson, Motoki Iwasaki, Rebecca D Jackson, Katarina Jood, Pekka Jousilahti, Sara Kaffashian, Lalit Kalra, Masahiro Kamouchi, Takanari Kitazono, Olafur Kjartansson, Manja Kloss, Peter J Koudstaal, Jerzy Krupinski, Daniel L Labovitz, Cathy C Laurie, Christopher R Levi, Linxin Li, Lars Lind, Cecilia M Lindgren, Vasileios Lioutas, Yong Mei Liu, Oscar L Lopez, Hirata Makoto, Nicolas Martinez‐Majander, Koichi Matsuda, Naoko Minegishi, Joan Montaner, Andrew P Morris, Elena Muiño, Martina Müller‐Nurasyid, Bo Norrving, Soichi Ogishima, Eugenio A Parati, Leema Reddy Peddareddygari, Nancy L Pedersen, Joanna Pera, Markus Perola, Alessandro Pezzini, Silvana Pileggi, Raquel Rabionet, Iolanda Riba‐Llena, Marta Ribasés, Jose R Romero, Jaume Roquer, Anthony G Rudd, Antti‐Pekka Sarin, Ralhan Sarju, Chloe Sarnowski, Makoto Sasaki, Claudia L Satizabal, Mamoru Satoh, Naveed Sattar, Norie Sawada, Gerli Sibolt, Ásgeir Sigurdsson, Albert Smith, Kenji Sobue, Carolina Soriano‐Tárraga, Tara Stanne, O Colin Stine, David J Stott, Konstantin Strauch, Takako Takai, Hideo Tanaka, Kozo Tanno, Alexander Teumer, Liisa Tomppo, Nuria P Torres‐Aguila, Emmanuel Touze, Shoichiro Tsugane, Andre G Uitterlinden, Einar M Valdimarsson, Sven J van der Lee, Henry Völzke, Kenji Wakai, David Weir, Stephen R Williams, Charles DA Wolfe, Quenna Wong, Huichun Xu, Taiki Yamaji, Dharambir K Sanghera, Olle Melander, Christina Jern, Daniel Strbian, Israel Fernandez‐Cadenas, W T Longstreth, Arndt Rolfs, Jun Hata, Daniel Woo, Jonathan Rosand, Guillaume Pare, Jemma C Hopewell, Danish Saleheen, Kari Stefansson, Bradford B Worrall, Steven J Kittner, Sudha Seshadri, Myriam Fornage, Hugh S Markus, Joanna MM Howson, Yoichiro Kamatani, Stephanie Debette, Martin Dichgans, and VU University medical center

Subjects
Hemostasis, genome-wide association study, genetic pleiotropy, Hematology, Polymorphism, Single Nucleotide, Hemostatics, blood coagulation, cardiovascular diseases, Phenotype, Cardiovascular Diseases, Tissue Plasminogen Activator, hemostasis, Humans, Genetic Predisposition to Disease, Factor XI, Genome-Wide Association Study
Abstract

Background: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. Objectives: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10−9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27). Results: Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. Conclusions: The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.

Published
2022
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