ePrints

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

Lookup NU author(s): Professor Mark Walker

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

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.

Publication metadata

Author(s): den Hoed M, Eijgelsheim M, Esko T, Brundel BJJM, Peal DS, Evans DM, Nolte IM, Segre AV, Holm H, Handsaker RE, Westra HJ, Johnson T, Isaacs A, Yang J, Lundby A, Zhao JH, Kim YJ, Go MJ, Almgren P, Bochud M, Boucher G, Cornelis MC, Gudbjartsson D, Hadley D, van der Harst P, Hayward C, den Heijer M, Igl W, Jackson AU, Kutalik Z, Luan J, Kemp JP, Kristiansson K, Ladenvall C, Lorentzon M, Montasser ME, Njajou OT, O'Reilly PF, Padmanabhan S, Pourcain BS, Rankinen T, Salo P, Tanaka T, Timpson NJ, Vitart V, Waite L, Wheeler W, Zhang WH, Draisma HHM, Feitosa MF, Kerr KF, Lind PA, Mihailov E, Onland-Moret NC, Song C, Weedon MN, Xie WJ, Yengo L, Absher D, Albert CM, Alonso A, Arking DE, de Bakker PIW, Balkau B, Barlassina C, Benaglio P, Bis JC, Bouatia-Naji N, Brage S, Chanock SJ, Chines PS, Chung M, Darbar D, Dina C, Dorr M, Elliott P, Felix SB, Fischer K, Fuchsberger C, de Geus EJC, Goyette P, Gudnason V, Harris TB, Hartikainen AL, Havulinna AS, Heckbert SR, Hicks AA, Hofman A, Holewijn S, Hoogstra-Berends F, Hottenga JJ, Jensen MK, Johansson A, Junttila J, Kaab S, Kanon B, Ketkar S, Khaw KT, Knowles JW, Kooner AS, Kors JA, Kumari M, Milani L, Laiho P, Lakatta EG, Langenberg C, Leusink M, Liu YM, Luben RN, Lunetta KL, Lynch SN, Markus MRP, Marques-Vidal P, Leach IM, McArdle WL, McCarroll SA, Medland SE, Miller KA, Montgomery GW, Morrison AC, Muller-Nurasyid M, Navarro P, Nelis M, O'Connell JR, O'Donnell CJ, Ong KK, Newman AB, Peters A, Polasek O, Pouta A, Pramstaller PP, Psaty BM, Rao DC, Ring SM, Rossin EJ, Rudan D, Sanna S, Scott RA, Sehmi JS, Sharp S, Shin JT, Singleton AB, Smith AV, Soranzo N, Spector TD, Stewart C, Stringham HM, Tarasov KV, Uitterlinden AG, Vandenput L, Hwang SJ, Whitfield JB, Wijmenga C, Wild SH, Willemsen G, Wilson JF, Witteman JCM, Wong A, Wong QN, Jamshidi Y, Zitting P, Boer JMA, Boomsma DI, Borecki IB, van Duijn CM, Ekelund U, Forouhi NG, Froguel P, Hingorani A, Ingelsson E, Kivimaki M, Kronmal RA, Kuh D, Lind L, Martin NG, Oostra BA, Pedersen NL, Quertermous T, Rotter JI, van der Schouw YT, Verschuren WMM, Walker M, Albanes D, Arnar DO, Assimes TL, Bandinelli S, Boehnke M, de Boer RA, Bouchard C, Caulfield WLM, Chambers JC, Curhan G, Cusi D, Eriksson J, Ferrucci L, van Gilst WH, Glorioso N, de Graaf J, Groop L, Gyllensten U, Hsueh WC, Hu FB, Huikuri HV, Hunter DJ, Iribarren C, Isomaa B, Jarvelin MR, Jula A, Kahonen M, Kiemeney LA, van der Klauw MM, Kooner JS, Kraft P, Iacoviello L, Lehtimaki T, Lokki MLL, Mitchell BD, Navis G, Nieminen MS, Ohlsson C, Poulter NR, Qi L, Raitakari OT, Rimm EB, Rioux JD, Rizzi F, Rudan I, Salomaa V, Sever PS, Shields DC, Shuldiner AR, Sinisalo J, Stanton AV, Stolk RP, Strachan DP, Tardif JC, Thorsteinsdottir U, Tuomilehto J, van Veldhuisen DJ, Virtamo J, Viikari J, Vollenweider P, Waeber G, Widen E, Cho YS, Olsen JV, Visscher PM, Willer C, Franke L, Erdmann J, Thompson JR, Pfeufer A, Sotoodehnia N, Newton-Cheh C, Ellinor PT, Stricker BHC, Metspalu A, Perola M, Beckmann JS, Smith GD, Stefansson K, Wareham NJ, Munroe PB, Sibon OCM, Milan DJ, Snieder H, Samani NJ, Loos RJF, Global BPgen Consortium, CARDIoGRAM Consortium, PR GWGWAS Consortium, QRS GWGWAS Consortium, QT-IGCGC Consortium, CHARGE-AF Consortium

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2013

Volume: 45

Issue: 6

Pages: 621-631

Print publication date: 01/06/2013

Online publication date: 14/04/2013

Acceptance date: 21/03/2013

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ng.2610

DOI: 10.1038/ng.2610

Altmetrics

Funding

Share