Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders by 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, Leach Irene Mateo, McArdle Wendy L, McCarroll Steven A, Medland Sarah E, Miller Kathryn A, Montgomery Grant W, Morrison Alanna C, M Vuml Ller-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, Global BPgen Consortium, CARDIoGRAM Consortium, Erdmann Jeanette, Thompson John R, PR GWAS Consortium, Pfeufer Arne, QRS GWAS Consortium, Sotoodehnia Nona, QT-IGC Consortium, Newton-Cheh Christopher, CHARGE-AF Consortium, 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 in Nature genetics (2013). PubMed

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.

[ hide abstract ]

Discussed In Paper

Related In Paper

Variant Annotations

None.