1. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
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den Hoed, M, Eijgelsheim, M, Esko, T, Brundel, Bj, Peal, Ds, Evans, Dm, Nolte, Im, Segrè, 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, St Pourcain, B, Rankinen, T, Salo, P, Tanaka, T, Timpson, Nj, Vitart, V, Waite, L, Wheeler, W, Zhang, W, Draisma, Hh, 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 PI, 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 EJ, 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, Kääb, 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, Y, Luben, Rn, Lunetta, Kl, Lynch, Sn, Markus, Mr, 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, Sj, Whitfield, Jb, Wijmenga, C, Wild, Sh, Willemsen, G, Wilson, Jf, Witteman, Jc, Wong, A, Wong, Q, Jamshidi, Y, Zitting, P, Boer, Jm, 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, Wm, Walker, M, Albanes, D, Arnar, Do, Assimes, Tl, Bandinelli, S, Boehnke, M, de Boer RA, Bouchard, C, Caulfield, Wl, 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, Kähönen, M, Kiemeney, La, van der Klauw MM, Kooner, Js, Kraft, P, Iacoviello, Licia, Lehtimäki, T, Lokki, Ml, 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, 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, Bh, Metspalu, A, Perola, M, Beckmann, Js, Smith, Gd, Stefansson, K, Wareham, Nj, Munroe, Pb, Sibon, Oc, Milan, Dj, Snieder, H, Samani, Nj, Loos, R. J., Global BPgen Consortium, CARDIoGRAM Consortium, PR GWAS Consortium, QRS GWAS Consortium, QT-IGC Consortium, CHARGE-AF Consortium, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Neuroscience Campus Amsterdam - Brain Imaging Technology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Humane Biologie, Epidemiology, Public Health, Clinical Genetics, Surgery, Medical Informatics, Internal Medicine, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, ICaR - Circulation and metabolism, EMGO - Lifestyle, overweight and diabetes, NCA - Brain imaging technology, ACS - Heart failure & arrhythmias, Physiology, Internal medicine, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Molecular Neuroscience and Ageing Research (MOLAR), and Stem Cell Aging Leukemia and Lymphoma (SALL)
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Netherlands Twin Register (NTR) ,Aetiology, screening and detection [ONCOL 5] ,030204 cardiovascular system & hematology ,Arrhythmias ,DISEASE ,Sudden cardiac death ,PR INTERVAL ,0302 clinical medicine ,Gene Frequency ,Heart Rate ,Arrhythmias, Cardiac/genetics ,0303 health sciences ,COMMON VARIANTS ,Dilated cardiomyopathy ,Atrial fibrillation ,Single Nucleotide ,Heart Rate/genetics ,3. Good health ,DROSOPHILA ,LIBRARY ,Cardiology ,QRS DURATION ,Electrical conduction system of the heart ,Metabolic Networks and Pathways ,rhytm ,conduction ,gene ,medicine.medical_specialty ,SUSCEPTIBILITY LOCI ,Quantitative Trait Loci ,Cardiac/genetics ,Biology ,Polymorphism, Single Nucleotide ,Article ,Sick sinus syndrome ,Heart Conduction System/physiopathology ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Heart Conduction System ,Internal medicine ,Cardiac conduction ,Heart rate ,Genetics ,medicine ,Animals ,Humans ,GENOME-WIDE ASSOCIATION ,Polymorphism ,Health aging / healthy living Cardiovascular diseases [IGMD 5] ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,030304 developmental biology ,QT INTERVAL ,Arrhythmias, Cardiac ,ta3121 ,medicine.disease ,Endocrinology ,Genetic Loci ,Heart failure ,ATRIAL-FIBRILLATION ,Genome-Wide Association Study - 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. © 2013 Nature America, Inc. All rights reserved.
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- 2013