| Title: |
Identification of heart rate–associated loci and their effects on cardiac conduction and rhythm disorders |
| Authors: |
den Hoed, Marcel; Eijgelsheim, Mark; Esko, Tõnu; Brundel, Bianca, J J M; Peal, David, S; Evans, David, M; Nolte, Ilja, M; Segrè, Ayellet, V; Holm, Hilma; Handsaker, Robert, E; Westra, Harm-Jan; Johnson, Toby; Isaacs, Aaron; Yang, Jian; Lundby, Alicia; Zhao, Jing Hua; Kim, Young Jin; Go, Min Jin; Almgren, Peter; Bochud, Murielle; Boucher, Gabrielle; Cornelis, Marilyn, C; Gudbjartsson, Daniel; Hadley, David; van der Harst, Pim; Hayward, Caroline; den Heijer, Martin; Igl, Wilmar; Jackson, Anne, U; Kutalik, Zoltán; Luan, Jian'An; Kemp, John, P; Kristiansson, Kati; Ladenvall, Claes; Lorentzon, Mattias; Montasser, May, E; Njajou, Omer, T; O'Reilly, Paul, F; Padmanabhan, Sandosh; St. Pourcain, Beate; Rankinen, Tuomo; Salo, Perttu; Tanaka, Toshiko; Timpson, Nicholas, J; Vitart, Veronique; Waite, Lindsay; Wheeler, William; Zhang, Weihua; Draisma, Harmen, H M; Feitosa, Mary, F; Kerr, Kathleen, F; Lind, Penelope, A; Mihailov, Evelin; Onland-Moret, N Charlotte; Song, Ci; Weedon, Michael, N; Xie, Weijia; Yengo, Loic; Absher, Devin; Albert, Christine, M; Alonso, Alvaro; Arking, Dan, E; de Bakker, Paul, I W; Balkau, Beverley; Barlassina, Cristina; Benaglio, Paola; Bis, Joshua, C; Bouatia-Naji, Nabila; Brage, Søren; Chanock, Stephen, J; Chines, Peter, S; Chung, Mina; Darbar, Dawood; Dina, Christian; Dörr, Marcus; Elliott, Paul; Felix, Stephan, B; Fischer, Krista; Fuchsberger, Christian; de Geus, Eco, J C; Goyette, Philippe; Gudnason, Vilmundur; Harris, Tamara, B; Hartikainen, Anna-Liisa; Havulinna, Aki, S; Heckbert, Susan, R; Hicks, Andrew, A; Hofman, Albert; Holewijn, Suzanne; Hoogstra-Berends, Femke; Hottenga, Jouke-Jan; Jensen, Majken, K; Johansson, Åsa; Junttila, Juhani; Kääb, Stefan; Kanon, Bart; Ketkar, Shamika; Khaw, Kay-Tee; Knowles, Joshua, W; Kooner, Angrad, S; Kors, Jan, A; Kumari, Meena; Milani, Lili; Laiho, Päivi; Lakatta, Edward, G; Langenberg, Claudia; Leusink, Maarten; Liu, Yongmei; Luben, Robert, N; Lunetta, Kathryn, L; Lynch, Stacey, N; Markus, Marcello, R P; Marques-Vidal, Pedro; Leach, Irene Mateo; Mcardle, Wendy, L; Mccarroll, Steven, A; Medland, Sarah, E; Miller, Kathryn, A; Montgomery, Grant, W; Morrison, Alanna, C; Müller-Nurasyid, Martina; Navarro, Pau; Nelis, Mari; O'Connell, Jeffrey, R; O'Donnell, Christopher, J; Ong, Ken, K; Newman, Anne, B; Peters, Annette; Polasek, Ozren; Pouta, Anneli; Pramstaller, Peter, P; Psaty, Bruce, M; Rao, Dabeeru, C; Ring, Susan, M; Rossin, Elizabeth, J; Rudan, Diana; Sanna, Serena; Scott, Robert, A; Sehmi, Jaban, S; Sharp, Stephen; Shin, Jordan, T; Singleton, Andrew, B; Smith, Albert, V; Soranzo, Nicole; Spector, Tim, D; Stewart, Chip; Stringham, Heather, M; Tarasov, Kirill, V; Uitterlinden, André, G; Vandenput, Liesbeth; Hwang, Shih-Jen; Whitfield, John, B; Wijmenga, Cisca; Wild, Sarah, H; Willemsen, Gonneke; Wilson, James, F; Witteman, Jacqueline, C M; Wong, Andrew; Wong, Quenna; Jamshidi, Yalda; Zitting, Paavo; Boer, Jolanda, M A; Boomsma, Dorret, I; Borecki, Ingrid, B; van Duijn, Cornelia, M; Ekelund, Ulf; Forouhi, Nita, G; Froguel, Philippe; Hingorani, Aroon; Ingelsson, Erik; Kivimaki, Mika; Kronmal, Richard, A; Kuh, Diana; Lind, Lars; Martin, Nicholas, G; Oostra, Ben, A; Pedersen, Nancy, L; Quertermous, Thomas; Rotter, Jerome, I; van der Schouw, Yvonne, T; Verschuren, W, M Monique; Walker, Mark; Albanes, Demetrius; Arnar, David, O; Assimes, Themistocles, L; Bandinelli, Stefania; Boehnke, Michael; de Boer, Rudolf, A; Bouchard, Claude; Caulfield, W, L Mark; Chambers, John, C; Curhan, Gary; Cusi, Daniele; Eriksson, Johan; Ferrucci, Luigi; van Gilst, Wiek, H; Glorioso, Nicola; de Graaf, Jacqueline; Groop, Leif; Gyllensten, Ulf; Hsueh, Wen-Chi; Hu, Frank, B; Huikuri, Heikki, V; Hunter, David, J; Iribarren, Carlos; Isomaa, Bo; Jarvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kiemeney, Lambertus, A; van der Klauw, Melanie, M; Kooner, Jaspal, S; Kraft, Peter; Iacoviello, Licia; Lehtimäki, Terho; Lokki, Marja-Liisa, L; Mitchell, Braxton, D; Navis, Gerjan; Nieminen, Markku, S; Ohlsson, Claes; Poulter, Neil, R; Qi, Lu; Raitakari, Olli, T; Rimm, Eric, B; Rioux, John, D; Rizzi, Federica; Rudan, Igor; Salomaa, Veikko; Sever, Peter, S; Shields, Denis, C; Shuldiner, Alan, R; Sinisalo, Juha; Stanton, Alice, V; Stolk, Ronald, P; Strachan, David, P; Tardif, Jean-Claude; Thorsteinsdottir, Unnur; Tuomilehto, Jaako; van Veldhuisen, Dirk, J; Virtamo, Jarmo; Viikari, Jorma; Vollenweider, Peter; Waeber, Gérard; Widen, Elisabeth; Cho, Yoon Shin; Olsen, Jesper, V; Visscher, Peter, M; Willer, Cristen; Franke, Lude; Erdmann, Jeanette; Thompson, John, R; Pfeufer, Arne; Sotoodehnia, Nona; Newton-Cheh, Christopher; Ellinor, Patrick, T; Stricker, Bruno, H Ch; Metspalu, Andres; Perola, Markus; Beckmann, Jacques, S; Smith, George Davey; Stefansson, Kari; Wareham, Nicholas, J; Munroe, Patricia, B; Sibon, Ody, C M; Milan, David, J; Snieder, Harold; Samani, Nilesh, J; Loos, Ruth, J F |
| Contributors: |
Tartu University Hospital; Amsterdam University Medical Centers (Amsterdam UMC); Harvard Medical School Boston (HMS); Department of Health Systems Financing; Organisation Mondiale de la Santé / World Health Organization Office Genève, Suisse (OMS / WHO); University of Groningen Groningen; Broad Institute of MIT and Harvard (BROAD INSTITUTE); Harvard Medical School Boston (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital Boston; deCODE genetics Reykjavik; Queen Mary University of London (QMUL); Centre for Medical Systems Biology; Erasmus University Rotterdam; Guangxi University Nanning (GXU); Københavns Universitet = University of Copenhagen = Université de Copenhague (UCPH); Institute of metabolic Science, MRC Epidemiology Unit; Addenbrooke's Hospital; Osong Health Technology Administration Complex; Partenaires INRAE; Department of Medical Epidemiology and Biostatistics (MEB); Karolinska Institutet = Karolinska Institute Stockholm; Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital Lausanne (CHUV); Université de Lausanne = University of Lausanne (UNIL); Centre de recherche en épidémiologie et santé des populations (CESP); Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse; AP-HP. Université Paris Saclay-AP-HP. Université Paris Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay; Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS); Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)); Hôpital Européen Georges Pompidou APHP (HEGP); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); ITX - unité de recherche de l'institut du thorax (ITX); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN); CZB/4/710/CSO_/Chief Scientist Office/United KingdomG0801056/MRC_/Medical Research Council/United KingdomMC_UU_12013/3/MRC_/Medical Research Council/United KingdomG1000143/MRC_/Medical Research Council/United KingdomMC_U106179471/MRC_/Medical Research Council/United KingdomG0401527/MRC_/Medical Research Council/United KingdomP30 DK020572/DK/NIDDK NIH HHS/United StatesMC_U127592696/MRC_/Medical Research Council/United KingdomMC_U106188470/MRC_/Medical Research Council/United KingdomPG/12/38/29615/BHF_/British Heart Foundation/United KingdomG9815508/MRC_/Medical Research Council/United KingdomK24 HL105780/HL/NHLBI NIH HHS/United StatesR01 HL092217/HL/NHLBI NIH HHS/United StatesG0600705/MRC_/Medical Research Council/United KingdomMC_UP_A100_1003/MRC_/Medical Research Council/United KingdomU19 HL065962/HL/NHLBI NIH HHS/United States092731/WT_/Wellcome Trust/United KingdomT32 GM007753/GM/NIGMS NIH HHS/United StatesMC_U106179473/MRC_/Medical Research Council/United KingdomUL1 TR000124/TR/NCATS NIH HHS/United StatesR01 HL090620/HL/NHLBI NIH HHS/United StatesR01 HL105756/HL/NHLBI NIH HHS/United StatesP30 DK063491/DK/NIDDK NIH HHS/United StatesMC_UU_12015/2/MRC_/Medical Research Council/United KingdomR21 DA026982/DA/NIDA NIH HHS/United StatesMC_PC_15018/MRC_/Medical Research Council/United KingdomMC_U123092720/MRC_/Medical Research Council/United KingdomMC_U106179472/MRC_/Medical Research Council/United KingdomG1002084/MRC_/Medical Research Council/United KingdomMC_PC_U127592696/MRC_/Medical Research Council/United KingdomMC_UU_12013/1/MRC_/Medical Research Council/United KingdomR01 HL111314/HL/NHLBI NIH HHS/United StatesR00 HL094535/HL/NHLBI NIH HHS/United StatesMC_UU_12013/4/MRC_/Medical Research Council/United KingdomMC_PC_U127561128/MRC_/Medical Research Council/United Kingdom |
| Source: |
ISSN: 1061-4036. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2013 |
| Collection: |
Université de Nantes: HAL-UNIV-NANTES |
| Subject Terms: |
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system; [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics; [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE]; [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/ng.2610 |
| Availability: |
https://hal.science/hal-05162454; https://doi.org/10.1038/ng.2610 |
| Rights: |
https://hal.science/licences/copyright/ |
| Accession Number: |
edsbas.1CC2CD61 |
| Database: |
BASE |