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

Marcel den Hoed, Mark Eijgelsheim, Tonu Esko, Bianca J. J. M. Brundel, David S. Peal, David M. Evans, Ilja M. Nolte, Ayellet V. Segre, Hilma Holm, Robert E. Handsaker, Harm-Jan Westra, Toby Johnson, Aaron Isaacs, Jian Yang, Alicia Lundby, Jing Hua Zhao, Young Jin Kim, Min Jin Go, Peter Almgren, Murielle BochudGabrielle Boucher, Marilyn C. Cornelis, Daniel Gudbjartsson, David Hadley, Pim van der Harst, Caroline Hayward, Martin den Heijer, Wilmar Igl, Anne U. Jackson, Zoltan Kutalik, Jian'an Luan, John P. Kemp, Kati Kristiansson, Claes Ladenvall, Mattias Lorentzon, May E. Montasser, Omer T. Njajou, Paul F. O'Reilly, Sandosh Padmanabhan, Beate St. Pourcain, Tuomo Rankinen, Perttu Salo, Toshiko Tanaka, Nicholas J. Timpson, Veronique Vitart, Lindsay Waite, William Wheeler, Weihua Zhang, Harmen H. M. Draisma, Mary F. Feitosa, Kathleen F. Kerr, Penelope A. Lind, Evelin Mihailov, N. Charlotte Onland-Moret, Ci Song, Michael N. Weedon, Weijia Xie, Loic Yengo, Devin Absher, Christine M. Albert, Alvaro Alonso, Dan E. Arking, Paul I. W. de Bakker, Beverley Balkau, Cristina Barlassina, Paola Benaglio, Joshua C. Bis, Nabila Bouatia-Naji, Soren Brage, Stephen J. Chanock, Peter S. Chines, Mina Chung, Dawood Darbar, Christian Dina, Marcus Doerr, Paul Elliott, Stephan B. Felix, Krista Fischer, Christian Fuchsberger, Eco J. C. de Geus, Philippe Goyette, Vilmundur Gudnason, Tamara B. Harris, Anna-Liisa Hartikainen, Aki S. Havulinna, Susan R. Heckbert, Andrew A. Hicks, Albert Hofman, Suzanne Holewijn, Femke Hoogstra-Berends, Jouke-Jan Hottenga, Majken K. Jensen, Asa Johansson, Juhani Junttila, Stefan Kaeaeb, Bart Kanon, Shamika Ketkar, Kay-Tee Khaw, Joshua W. Knowles, Angrad S. Kooner, Jan A. Kors, Meena Kumari, Lili Milani, Paeivi Laiho, Edward G. Lakatta, Claudia Langenberg, Maarten Leusink, Yongmei Liu, Robert N. Luben, Kathryn L. Lunetta, Stacey N. Lynch, Marcello R. P. Markus, Pedro Marques-Vidal, Irene Mateo Leach, Wendy L. McArdle, Steven A. McCarroll, Sarah E. Medland, Kathryn A. Miller, Grant W. Montgomery, Alanna C. Morrison, Martina Mueller-Nurasyid, Pau Navarro, Mari Nelis, Jeffrey R. O'Connell, Christopher J. O'Donnell, Ken K. Ong, Anne B. Newman, Annette Peters, Ozren Polasek, Anneli Pouta, Peter P. Pramstaller, Bruce M. Psaty, Dabeeru C. Rao, Susan M. Ring, Elizabeth J. Rossin, Diana Rudan, Serena Sanna, Robert A. Scott, Jaban S. Sehmi, Stephen Sharp, Jordan T. Shin, Andrew B. Singleton, Albert V. Smith, Nicole Soranzo, Tim D. Spector, Chip Stewart, Heather M. Stringham, Kirill V. Tarasov, Andre G. Uitterlinden, Liesbeth Vandenput, Shih-Jen Hwang, John B. Whitfield, Cisca Wijmenga, Sarah H. Wild, Gonneke Willemsen, James F. Wilson, Jacqueline C. M. Witteman, Andrew Wong, Quenna Wong, Yalda Jamshidi, Paavo Zitting, Jolanda M. A. Boer, Dorret I. Boomsma, Ingrid B. Borecki, Cornelia M. van Duijn, Ulf Ekelund, Nita G. Forouhi, Philippe Froguel, Aroon Hingorani, Erik Ingelsson, Mika Kivimaki, Richard A. Kronmal, Diana Kuh, Lars Lind, Nicholas G. Martin, Ben A. Oostra, Nancy L. Pedersen, Thomas Quertermous, Jerome I. Rotter, Yvonne T. van der Schouw, W. M. Monique Verschuren, Mark Walker, Demetrius Albanes, David O. Arnar, Themistocles L. Assimes, Stefania Bandinelli, Michael Boehnke, Rudolf A. de Boer, Claude Bouchard, W. L. Mark Caulfield, John C. Chambers, Gary Curhan, Daniele Cusi, Johan Eriksson, Luigi Ferrucci, Wiek H. van Gilst, Nicola Glorioso, Jacqueline de Graaf, Leif Groop, Ulf Gyllensten, Wen-Chi Hsueh, Frank B. Hu, Heikki V. Huikuri, David J. Hunter, Carlos Iribarren, Bo Isomaa, Marjo-Riitta Jarvelin, Antti Jula, Mika Kahonen, Lambertus A. Kiemeney, Melanie M. van der Klauw, Jaspal S. Kooner, Peter Kraft, Licia Iacoviello, Terho Lehtimaki, Marja-Liisa L. Lokki, Braxton D. Mitchell, Gerjan Navis, Markku S. Nieminen, Claes Ohlsson, Neil R. Poulter, Lu Qi, Olli T. Raitakari, Eric B. Rimm, John D. Rioux, Federica Rizzi, Igor Rudan, Veikko Salomaa, Peter S. Sever, Denis C. Shields, Alan R. Shuldiner, Juha Sinisalo, Alice V. Stanton, Ronald P. Stolk, David P. Strachan, Jean-Claude Tardif, Unnur Thorsteinsdottir, Jaako Tuomilehto, Dirk J. van Veldhuisen, Jarmo Virtamo, Jorma Viikari, Peter Vollenweider, Gerard Waeber, Elisabeth Widen, Yoon Shin Cho, Jesper V. Olsen, Peter M. Visscher, Cristen Willer, Lude Franke, Jeanette Erdmann, John R. Thompson, Arne Pfeufer, Nona Sotoodehnia, Christopher Newton-Cheh, Patrick T. Ellinor, Bruno H. Ch Stricker, Andres Metspalu, Markus Perola, Jacques S. Beckmann, George Davey Smith, Kari Stefansson, Nicholas J. Wareham, Patricia B. Munroe, Ody C. M. Sibon, David J. Milan, Harold Snieder, Nilesh J. Samani, Ruth J. F. Loos

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

208 Citeringar (SciVal)

Sammanfattning

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.
Originalspråkengelska
Sidor (från-till)621-631
TidskriftNature Genetics
Volym45
Utgåva6
DOI
StatusPublished - 2013

Ämnesklassifikation (UKÄ)

  • Endokrinologi och diabetes

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