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Genetic loci associated with heart rate variability and their effects on cardiac disease risk
| File | Description | Size | Format | |
|---|---|---|---|---|
 ncomms15805.pdf | Published version | 528.43 kB | Adobe PDF | View/Open |
| Title: | Genetic loci associated with heart rate variability and their effects on cardiac disease risk |
| Authors: | Nolte, IM Munoz, ML Tragante, V Amare, AT Jansen, R Vaez, A Von der Heyde, B Avery, CL Bis, JC Dierckx, B Van Dongen, J Gogarten, SM Goyette, P Hernesniemi, J Huikari, V Hwang, S-J Jaju, D Kerr, KF Kluttig, A Krijthe, BP Kumar, J Van der Laan, SW Lyytikainen, L-P Maihofer, AX Minassian, A Van der Most, PJ Mueller-Nurasyid, M Nivard, M Salvi, E Stewart, JD Thayer, JF Verweij, N Wong, A Zabaneh, D Zafarmand, MH Abdellaoui, A Albarwani, S Albert, C Alonso, A Ashar, F Auvinen, J Axelsson, T Baker, DG De Bakker, PIW Barcella, M Bayoumi, R Bieringa, RJ Boomsma, D Boucher, G Britton, AR Christophersen, IE Dietrich, A Ehret, GB Ellinor, PT Eskola, M Felix, JF Floras, JS Franco, OH Friberg, P Gademan, MGJ Geyer, MA Giedraitis, V Hartman, CA Hemerich, D Hofman, A Hottenga, J-J Huikuri, H Hutri-Kahonen, N Jouven, X Junttila, J Juonala, M Kiviniemi, AM Kors, JA Kumari, M Kuznetsova, T Laurie, CC Lefrandt, JD Li, Y Li, Y Liao, D Limacher, MC Lin, HJ Lindgren, CM Lubitz, SA Mahajan, A McKnight, B Zu Schwabedissen, HM Milaneschi, Y Mononen, N Morris, AP Nalls, MA Navis, G Neijts, M Nikus, K North, KE O'Connor, DT Ormel, J Perz, S Peters, A Psaty, BM Raitakari, OT Risbrough, VB Sinner, MF Siscovick, D Smit, JH Smith, NL Soliman, EZ Sotoodehnia, N Staessen, JA Stein, PK Stilp, AM Stolarz-Skrzypek, K Strauch, K Sundstrom, J Swenne, CA Syvanen, A-C Tardif, J-C Taylor, KD Teumer, A Thornton, TA Tinker, LE Uitterlinden, AG Van Setten, J Voss, A Waldenberger, M Wilhelmsen, KC Willemsen, G Wong, Q Zhang, Z-M Zonderman, AB Cusi, D Evans, MK Greiser, HK Van der Harst, P Hassan, M Ingelsson, E Jarvelin, M-R Kaab, S Kahonen, M Kivimaki, M Kooperberg, C Kuh, D Lehtimaki, T Lind, L Nievergelt, CM O'Donnell, CJ Oldehinkel, AJ Penninx, B Reiner, AP Riese, H Van Roon, AM Rioux, JD Rotter, JI Sofer, T Stricker, BH Tiemeier, H Vrijkotte, TGM Asselbergs, FW Brundel, BJJM Heckbert, SR Whitsel, EA Den Hoed, M Snieder, H De Geus, EJC |
| Item Type: | Journal Article |
| Abstract: | Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (−0.74<rg<−0.55) and blood pressure (−0.35<rg<−0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization. |
| Issue Date: | 14-Jun-2017 |
| Date of Acceptance: | 8-May-2017 |
| URI: | http://hdl.handle.net/10044/1/49946 |
| DOI: | https://dx.doi.org/10.1038/ncomms15805 |
| ISSN: | 2041-1723 |
| Publisher: | NATURE PUBLISHING GROUP |
| Journal / Book Title: | NATURE COMMUNICATIONS |
| Volume: | 8 |
| Copyright Statement: | © 2017 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/ |
| Keywords: | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics GENOME-WIDE ASSOCIATION RESPIRATORY SINUS ARRHYTHMIA PARASYMPATHETIC REGULATION ATRIAL-FIBRILLATION METAANALYSIS MORTALITY COHORT RECORDINGS MODULATOR PEDIGREES MD Multidisciplinary |
| Publication Status: | Published |
| Article Number: | ARTN 15805 |
| Appears in Collections: | School of Public Health |