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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • June 2013

Published In

Volume / Issue

  • 45 / 6

Start / End Page

  • 621 - 631

PubMed ID

  • 23583979

Pubmed Central ID

  • 23583979

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.2610

Language

  • eng

Conference Location

  • United States