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

Publication ,  Journal Article
den Hoed, M; Eijgelsheim, M; Esko, T; Brundel, BJJM; Peal, DS; Evans, DM; Nolte, IM; Segrè, AV; Holm, H; Handsaker, RE; Westra, H-J; Isaacs, A ...
Published in: Nat Genet
June 2013

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.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

June 2013

Volume

45

Issue

6

Start / End Page

621 / 631

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Metabolic Networks and Pathways
  • Humans
  • Heart Rate
  • Heart Conduction System
  • Genome-Wide Association Study
  • Genetic Loci
  • Gene Frequency
  • Developmental Biology
 

Citation

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den Hoed, M., Eijgelsheim, M., Esko, T., Brundel, B. J. J. M., Peal, D. S., Evans, D. M., … Loos, R. J. F. (2013). Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nat Genet, 45(6), 621–631. https://doi.org/10.1038/ng.2610
Hoed, Marcel den, Mark Eijgelsheim, Tõnu Esko, Bianca J. J. M. Brundel, David S. Peal, David M. Evans, Ilja M. Nolte, et al. “Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.Nat Genet 45, no. 6 (June 2013): 621–31. https://doi.org/10.1038/ng.2610.
den Hoed M, Eijgelsheim M, Esko T, Brundel BJJM, Peal DS, Evans DM, et al. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nat Genet. 2013 Jun;45(6):621–31.
den Hoed, Marcel, et al. “Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.Nat Genet, vol. 45, no. 6, June 2013, pp. 621–31. Pubmed, doi:10.1038/ng.2610.
den Hoed M, Eijgelsheim M, Esko T, Brundel BJJM, Peal DS, Evans DM, Nolte IM, Segrè AV, Holm H, Handsaker RE, Westra H-J, 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, St Pourcain B, Rankinen T, Salo P, Tanaka T, Timpson NJ, Vitart V, Waite L, Wheeler W, Zhang W, Draisma HHM, Feitosa MF, Kerr KF, Lind PA, Mihailov E, Onland-Moret NC, Song C, Weedon MN, Xie W, 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, Dörr M, Elliott P, Felix SB, Fischer K, Fuchsberger C, de Geus EJC, Goyette P, Gudnason V, Harris TB, Hartikainen A-L, Havulinna AS, Heckbert SR, Hicks AA, Hofman A, Holewijn S, Hoogstra-Berends F, Hottenga J-J, Jensen MK, Johansson A, Junttila J, Kääb S, Kanon B, Ketkar S, Khaw K-T, Knowles JW, Kooner AS, Kors JA, Kumari M, Milani L, Laiho P, Lakatta EG, Langenberg C, Leusink M, Liu Y, Luben RN, Lunetta KL, Lynch SN, Markus MRP, Marques-Vidal P, Mateo Leach I, McArdle WL, McCarroll SA, Medland SE, Miller KA, Montgomery GW, Morrison AC, Müller-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 S-J, Whitfield JB, Wijmenga C, Wild SH, Willemsen G, Wilson JF, Witteman JCM, Wong A, Wong Q, 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 W-C, Hu FB, Huikuri HV, Hunter DJ, Iribarren C, Isomaa B, Jarvelin M-R, Jula A, Kähönen M, Kiemeney LA, van der Klauw MM, Kooner JS, Kraft P, Iacoviello L, Lehtimäki T, Lokki M-LL, 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 J-C, 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, Global BPgen Consortium, CARDIoGRAM Consortium, Erdmann J, Thompson JR, PR GWAS Consortium, Pfeufer A, QRS GWAS Consortium, Sotoodehnia N, QT-IGC Consortium, Newton-Cheh C, CHARGE-AF Consortium, 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. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nat Genet. 2013 Jun;45(6):621–631.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

June 2013

Volume

45

Issue

6

Start / End Page

621 / 631

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Metabolic Networks and Pathways
  • Humans
  • Heart Rate
  • Heart Conduction System
  • Genome-Wide Association Study
  • Genetic Loci
  • Gene Frequency
  • Developmental Biology