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Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders

den Hoed, Marcel; Eijgelsheim, Mark; Esko, Tonu; Brundel, Bianca J. J. M.; Peal, David S.; Evans, David M.; Nolte, Ilja M.; Segre, Ayellet V.; Holm, Hilma and Handsaker, Robert E., et al. (2013) In Nature Genetics 45(6). p.621-631
Abstract
Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is... (More)
Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets. (Less)
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Nature Genetics
volume
45
issue
6
pages
621 - 631
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Nature Publishing Group
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  • wos:000319563900009
  • scopus:84878726099
ISSN
1546-1718
DOI
10.1038/ng.2610
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English
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b9c8f7e5-905f-496f-8c0f-1330ccdc716d (old id 3930746)
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2013-07-16 09:59:17
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2019-03-17 04:08:54
@article{b9c8f7e5-905f-496f-8c0f-1330ccdc716d,
  abstract     = {Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.},
  author       = {den Hoed, Marcel and Eijgelsheim, Mark and Esko, Tonu and Brundel, Bianca J. J. M. and Peal, David S. and Evans, David M. and Nolte, Ilja M. and Segre, Ayellet V. and Holm, Hilma and Handsaker, Robert E. and Westra, Harm-Jan and Johnson, Toby and Isaacs, Aaron and Yang, Jian and Lundby, Alicia and Zhao, Jing Hua and Kim, Young Jin and Go, Min Jin and Almgren, Peter and Bochud, Murielle and Boucher, Gabrielle and Cornelis, Marilyn C. and Gudbjartsson, Daniel and Hadley, David and van der Harst, Pim and Hayward, Caroline and den Heijer, Martin and Igl, Wilmar and Jackson, Anne U. and Kutalik, Zoltan and Luan, Jian'an and Kemp, John P. and Kristiansson, Kati and Ladenvall, Claes and Lorentzon, Mattias and Montasser, May E. and Njajou, Omer T. and O'Reilly, Paul F. and Padmanabhan, Sandosh and Pourcain, Beate St. and Rankinen, Tuomo and Salo, Perttu and Tanaka, Toshiko and Timpson, Nicholas J. and Vitart, Veronique and Waite, Lindsay and Wheeler, William and Zhang, Weihua and Draisma, Harmen H. M. and Feitosa, Mary F. and Kerr, Kathleen F. and Lind, Penelope A. and Mihailov, Evelin and Onland-Moret, N. Charlotte and Song, Ci and Weedon, Michael N. and Xie, Weijia and Yengo, Loic and Absher, Devin and Albert, Christine M. and Alonso, Alvaro and Arking, Dan E. and de Bakker, Paul I. W. and Balkau, Beverley and Barlassina, Cristina and Benaglio, Paola and Bis, Joshua C. and Bouatia-Naji, Nabila and Brage, Soren and Chanock, Stephen J. and Chines, Peter S. and Chung, Mina and Darbar, Dawood and Dina, Christian and Doerr, Marcus and Elliott, Paul and Felix, Stephan B. and Fischer, Krista and Fuchsberger, Christian and de Geus, Eco J. C. and Goyette, Philippe and Gudnason, Vilmundur and Harris, Tamara B. and Hartikainen, Anna-Liisa and Havulinna, Aki S. and Heckbert, Susan R. and Hicks, Andrew A. and Hofman, Albert and Holewijn, Suzanne and Hoogstra-Berends, Femke and Hottenga, Jouke-Jan and Jensen, Majken K. and Johansson, Asa and Junttila, Juhani and Kaeaeb, Stefan and Kanon, Bart and Ketkar, Shamika and Khaw, Kay-Tee and Knowles, Joshua W. and Kooner, Angrad S. and Kors, Jan A. and Kumari, Meena and Milani, Lili and Laiho, Paeivi and Lakatta, Edward G. and Langenberg, Claudia and Leusink, Maarten and Liu, Yongmei and Luben, Robert N. and Lunetta, Kathryn L. and Lynch, Stacey N. and Markus, Marcello R. P. and Marques-Vidal, Pedro and Leach, Irene Mateo and McArdle, Wendy L. and McCarroll, Steven A. and Medland, Sarah E. and Miller, Kathryn A. and Montgomery, Grant W. and Morrison, Alanna C. and Mueller-Nurasyid, Martina and Navarro, Pau and Nelis, Mari and O'Connell, Jeffrey R. and O'Donnell, Christopher J. and Ong, Ken K. and Newman, Anne B. and Peters, Annette and Polasek, Ozren and Pouta, Anneli and Pramstaller, Peter P. and Psaty, Bruce M. and Rao, Dabeeru C. and Ring, Susan M. and Rossin, Elizabeth J. and Rudan, Diana and Sanna, Serena and Scott, Robert A. and Sehmi, Jaban S. and Sharp, Stephen and Shin, Jordan T. and Singleton, Andrew B. and Smith, Albert V. and Soranzo, Nicole and Spector, Tim D. and Stewart, Chip and Stringham, Heather M. and Tarasov, Kirill V. and Uitterlinden, Andre G. and Vandenput, Liesbeth and Hwang, Shih-Jen and Whitfield, John B. and Wijmenga, Cisca and Wild, Sarah H. and Willemsen, Gonneke and Wilson, James F. and Witteman, Jacqueline C. M. and Wong, Andrew and Wong, Quenna and Jamshidi, Yalda and Zitting, Paavo and Boer, Jolanda M. A. and Boomsma, Dorret I. and Borecki, Ingrid B. and van Duijn, Cornelia M. and Ekelund, Ulf and Forouhi, Nita G. and Froguel, Philippe and Hingorani, Aroon and Ingelsson, Erik and Kivimaki, Mika and Kronmal, Richard A. and Kuh, Diana and Lind, Lars and Martin, Nicholas G. and Oostra, Ben A. and Pedersen, Nancy L. and Quertermous, Thomas and Rotter, Jerome I. and van der Schouw, Yvonne T. and Verschuren, W. M. Monique and Walker, Mark and Albanes, Demetrius and Arnar, David O. and Assimes, Themistocles L. and Bandinelli, Stefania and Boehnke, Michael and de Boer, Rudolf A. and Bouchard, Claude and Caulfield, W. L. Mark and Chambers, John C. and Curhan, Gary and Cusi, Daniele and Eriksson, Johan and Ferrucci, Luigi and van Gilst, Wiek H. and Glorioso, Nicola and de Graaf, Jacqueline and Groop, Leif and Gyllensten, Ulf and Hsueh, Wen-Chi and Hu, Frank B. and Huikuri, Heikki V. and Hunter, David J. and Iribarren, Carlos and Isomaa, Bo and Jarvelin, Marjo-Riitta and Jula, Antti and Kahonen, Mika and Kiemeney, Lambertus A. and van der Klauw, Melanie M. and Kooner, Jaspal S. and Kraft, Peter and Iacoviello, Licia and Lehtimaki, Terho and Lokki, Marja-Liisa L. and Mitchell, Braxton D. and Navis, Gerjan and Nieminen, Markku S. and Ohlsson, Claes and Poulter, Neil R. and Qi, Lu and Raitakari, Olli T. and Rimm, Eric B. and Rioux, John D. and Rizzi, Federica and Rudan, Igor and Salomaa, Veikko and Sever, Peter S. and Shields, Denis C. and Shuldiner, Alan R. and Sinisalo, Juha and Stanton, Alice V. and Stolk, Ronald P. and Strachan, David P. and Tardif, Jean-Claude and Thorsteinsdottir, Unnur and Tuomilehto, Jaako and van Veldhuisen, Dirk J. and Virtamo, Jarmo and Viikari, Jorma and Vollenweider, Peter and Waeber, Gerard and Widen, Elisabeth and Cho, Yoon Shin and Olsen, Jesper V. and Visscher, Peter M. and Willer, Cristen and Franke, Lude and Erdmann, Jeanette and Thompson, John R. and Pfeufer, Arne and Sotoodehnia, Nona and Newton-Cheh, Christopher and Ellinor, Patrick T. and Stricker, Bruno H. Ch and Metspalu, Andres and Perola, Markus and Beckmann, Jacques S. and Smith, George Davey and Stefansson, Kari and Wareham, Nicholas J. and Munroe, Patricia B. and Sibon, Ody C. M. and Milan, David J. and Snieder, Harold and Samani, Nilesh J. and Loos, Ruth J. F.},
  issn         = {1546-1718},
  language     = {eng},
  number       = {6},
  pages        = {621--631},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders},
  url          = {http://dx.doi.org/10.1038/ng.2610},
  volume       = {45},
  year         = {2013},
}