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Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Nolte, IM. and Munoz, ML. and Tragante, V. and Amare, AT. and Jansen, R. and Vaez, A. and von der Heyde, B. and Avery, CL. and Bis, JC. and Dierckx, B. and van Dongen, J. and Gogarten, SM. and Goyette, P. and Hernesniemi, J. and Huikari, V. and Hwang, SJ. and Jaju, D. and Kerr, KF. and Kluttig, A. and Krijthe, BP. and Kumar, J. and van der Laan, SW. and Lyytikäinen, LP. and Maihofer, AX. and Minassian, A. and van der Most, PJ. and Müller-Nurasyid, M. and Nivard, M. and Salvi, E. and Stewart, JD. and Thayer, JF. and Verweij, N. and Wong, A. and Zabaneh, D. and Zafarmand, MH. and Abdellaoui, A. and Albarwani, S. and Albert, C. and Alonso, A. and Ashar, F. and Auvinen, J. and Axelsson, T. and Baker, DG. and de Bakker, PIW. and Barcella, M. and Bayoumi, R. and Bieringa, RJ. and Boomsma, D. and Boucher, G. and Britton, AR. and Christophersen, I. and Dietrich, A. and Ehret, GB. and Ellinor, PT. and Eskola, M. and Felix, JF. and Floras, JS. and Franco, OH. and Friberg, P. and Gademan, M. G. J. and Geyer, MA. and Giedraitis, V. and Hartman, CA. and Hemerich, D. and Hofman, A. and Hottenga, JJ. and Huikuri, H. and Hutri-Kähönen, N. and Jouven, X. and Junttila, J. and Juonala, M. and Kiviniemi, AM. and Kors, JA. and Kumari, M. and Kuznetsova, T. and Laurie, CC. and Lefrandt, JD. and Li, Y. and Li, Y. and Liao, D. and Limacher, MC. and Lin, HJ. and Lindgren, CM. and Lubitz, SA. and Mahajan, A. and McKnight, B. and Meyer zu Schwabedissen, HE. and Milaneschi, Y. and Mononen, N. and Morris, AP. and Nalls, MA. and Navis, G. and Neijts, M. and Nikus, K. and North, KE. and O'Connor, DT. and Ormel, J. and Perz, S. and Peters, A. and Psaty, BM. and Raitakari, OT. and Risbrough, VB. and Sinner, MF. and Siscovick, D. and Smit, JH. and Smith, NL. and Soliman, EZ. and Sotoodehnia, N. and Staessen, JA. and Stein, PK. and Stilp, AM. and Stolarz-Skrzypek, K. and Strauch, K. and Sundström, J. and Swenne, CA. and Syvänen, AC. and Tardif, JC. and Taylor, KD. and Teumer, A. and Thornton, TA. and Tinker, LE. and Uitterlinden, AG. and van Setten, J. and Voss, A. and Waldenberger, M. and Wilhelmsen, KC. and Willemsen, G. and Wong, Q. and Zhang, ZM. and Zonderman, AB. and Cusi, D. and Evans, MK. and Greiser, HK. and van der Harst, P. and Hassan, M. and Ingelsson, E. and Järvelin, MR. and Kääb, S. and Kähönen, M. and Kivimaki, M. and Kooperberg, C. and Kuh, D. and Lehtimäki, T. and Lind, L. and Nievergelt, CM. and O'Donnell, CJ. and Oldehinkel, AJ. and Penninx, B. and Reiner, AP. and Riese, H. and van Roon, AM. and Rioux, JD. and Rotter, JI. and Sofer, T. and Stricker, BH. and Tiemeier, H. and Vrijkotte, TGM. and Asselbergs, FW. and Brundel, Bjjm. and Heckbert, SR. and Whitsel, EA. and den Hoed, M. and Snieder, H. and de Geus, EJC.. (2017) Genetic loci associated with heart rate variability and their effects on cardiac disease risk. Nature Communications, 8. p. 15805.

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Official URL: https://edoc.unibas.ch/62974/

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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 (-0.74g>-0.55) and blood pressure (-0.35g<-0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rythm regulation, with a key role for genetic variants (GNG11,RGS6) that influence G-protein heterotrimer action in HIRK-channel induced pacemaker membrane hyperpolarization.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Biopharmazie (Meyer zu Schwabedissen)
UniBasel Contributors:Meyer zu Schwabedissen, H.
Item Type:Article, refereed
Article Subtype:Research Article
e-ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Mar 2019 19:09
Deposited On:26 Mar 2019 19:09

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