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Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
Monday,2019-04-22 17:18 America/Los_Angeles — ecterry
| Title | Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Hoed, Mden, 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, YJin, Go, MJ, Almgren, P, Bochud, M, Boucher, G, Cornelis, MC, Gudbjartsson, D, Hadley, D, van der Harst, P, Hayward, C, Heijer, Mden, Igl, W, Jackson, AU, Kutalik, Z, Luan, J'an, 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, CN, 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, Leach, IMateo, 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, WMMonique, Walker, M, Albanes, D, Arnar, DO, Assimes, TL, Bandinelli, S, Boehnke, M, de Boer, RA, Bouchard, C, Caulfield, WLMark, 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, Erdmann, J, Thompson, JR, Pfeufer, A, Sotoodehnia, N, Newton-Cheh, C, Ellinor, PT, Stricker, BHCh, Metspalu, A, Perola, M, Beckmann, JS, Smith, GD, Stefansson, K, Wareham, NJ, Munroe, PB, Sibon, OCM, Milan, DJ, Snieder, H, Samani, NJ, Loos, RJF |
| Corporate/Institutional Authors | Global BPgen Consortium, CARDIoGRAM consortium, PR GWAS Consortium, QRS GWAS Consortium, QT-IGC consortium, CHARGE-AF Consortium |
| Journal | Nat Genet |
| Volume | 45 |
| Issue | 6 |
| Pagination | 621-31 |
| Date Published | 2013 Jun |
| ISSN | 1546-1718 |
| Keywords | Animals, Arrhythmias, Cardiac, Gene Frequency, Genetic Loci, Genome-Wide Association Study, Heart Conduction System, Heart Rate, Humans, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Quantitative Trait Loci |
| Abstract | <p>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.</p> |
| DOI | 10.1038/ng.2610 |
| Alternate Journal | Nat. Genet. |
| PubMed ID | 23583979 |
| PubMed Central ID | PMC3696959 |
| Grant List | CZB/4/710 / / Chief Scientist Office / United Kingdom G0801056 / / Medical Research Council / United Kingdom K24 HL105780 / HL / NHLBI NIH HHS / United States R01 HL092217 / HL / NHLBI NIH HHS / United States G0600705 / / Medical Research Council / United Kingdom MC_UP_A100_1003 / / Medical Research Council / United Kingdom MC_UU_12013/3 / / Medical Research Council / United Kingdom U19 HL065962 / HL / NHLBI NIH HHS / United States 092731 / / Wellcome Trust / United Kingdom G1000143 / / Medical Research Council / United Kingdom T32 GM007753 / GM / NIGMS NIH HHS / United States MC_U106179473 / / Medical Research Council / United Kingdom UL1 TR000124 / TR / NCATS NIH HHS / United States R01 HL090620 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States MC_U106179471 / / Medical Research Council / United Kingdom P30 DK063491 / DK / NIDDK NIH HHS / United States MC_UU_12015/2 / / Medical Research Council / United Kingdom R21 DA026982 / DA / NIDA NIH HHS / United States MC_PC_15018 / / Medical Research Council / United Kingdom MC_U123092720 / / Medical Research Council / United Kingdom MC_U106179472 / / Medical Research Council / United Kingdom G1002084 / / Medical Research Council / United Kingdom MC_PC_U127592696 / / Medical Research Council / United Kingdom G0401527 / / Medical Research Council / United Kingdom MC_UU_12013/1 / / Medical Research Council / United Kingdom R01 HL111314 / HL / NHLBI NIH HHS / United States R00 HL094535 / HL / NHLBI NIH HHS / United States MC_UU_12013/4 / / Medical Research Council / United Kingdom MC_PC_U127561128 / / Medical Research Council / United Kingdom P30 DK020572 / DK / NIDDK NIH HHS / United States MC_U127592696 / / Medical Research Council / United Kingdom MC_U106188470 / / Medical Research Council / United Kingdom PG/12/38/29615 / / British Heart Foundation / United Kingdom G9815508 / / Medical Research Council / United Kingdom |
ePub date:
13/06