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

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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, Asa
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
Mateo Leach, Irene
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
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Issue Date
2013-06

Metadata
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Citation
Nat. Genet. 2013, 45 (6):621-31
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.
Description
To access publisher's full text version of this article click on the hyperlink at the bottom of the page
Additional Links
http://dx.doi.org/10.1038/ng.2610
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696959/
http://www.nature.com/ng/journal/v45/n6/pdf/ng.2610.pdf
Rights
Archived with thanks to Nature genetics
ae974a485f413a2113503eed53cd6c53
10.1038/ng.2610
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English Journal Articles (Peer Reviewed)

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