Genetic loci associated with heart rate variability and their effects on cardiac disease risk
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Publication date
2017-06-14
Authors
Nolte, Ilja M.
Munoz, M. Loretto
Tragante, Vinicius
Amare, Azmeraw T.
Jansen, Rick
Vaez, Ahmad
Von Der Heyde, Benedikt
Avery, Christy L.
Bis, Joshua C.
Dierckx, Bram
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Article
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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 (-0.74<r g <-0.55) and blood pressure (-0.35<r g <-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.
Keywords
General Chemistry, General Biochemistry,Genetics and Molecular Biology, General Physics and Astronomy, Journal Article
Citation
Nolte, I M, Munoz, M L, Tragante, V, Amare, A T, Jansen, R, Vaez, A, Von Der Heyde, B, Avery, C L, Bis, J C, Dierckx, B, van Dongen, J, Gogarten, S M, Goyette, P, Hernesniemi, J, Huikari, V, Hwang, S-J, Jaju, D, Kerr, K F, Kluttig, A, Krijthe, B P, Kumar, J, Van Der Laan, S W, Lyytikäinen, L-P, Maihofer, A X, Minassian, A, van der Most, P J, Müller-Nurasyid, M, Nivard, M G, Salvi, E, Stewart, J D, Thayer, J F, Verweij, N, Wong, A, Zabaneh, D, Zafarmand, M H, Abdellaoui, A, Albarwani, S, Albert, C, Alonso, A, Ashar, F N, Auvinen, J, Axelsson, T, Baker, D G, De Bakker, P I W, Barcella, M, Bayoumi, R, Bieringa, R J, Boomsma, D I, Boucher, G, Britton, A R, Christophersen, I E, Dietrich, A, Ehret, G B, Ellinor, P T, Eskola, M, Felix, J F, Floras, J S, Franco, O H, Friberg, P, Gademan, M G J, Geyer, M A, Giedraitis, V, Hartman, C A, Hemerich, D, Hofman, A, Hottenga, J-J, Huikuri, H V, Hutri-Kähönen, N, Jouven, X, Junttila, J, Juonala, M, Kiviniemi, A M, Kors, J A, Kumari, M, Kuznetsova, T, Laurie, C C, Lefrandt, J D, Li, Y, Li, Y R, Liao, D, Limacher, M C, Lin, H J, Lindgren, C M, Lubitz, S A, Mahajan, A, McKnight, B, Meyer Zu Schwabedissen, H, Milaneschi, Y, Mononen, N, Morris, A P, Nalls, M A, Navis, G J, Neijts, M, Nikus, K, North, K E, O'Connor, D T, Ormel, J, Perz, S, Peters, A, Psaty, B M, Raitakari, O T, Risbrough, V B, Sinner, M F, Siscovick, D S, Smit, J H, Smith, N L, Soliman, E Z, Sotoodehnia, N, Staessen, J A, Stein, P K, Stilp, A M, Stolarz-Skrzypek, K, Strauch, K, Sundström, J, Swenne, C A, Syvänen, A-C, Tardif, J-C, Taylor, K D, Teumer, A, Thornton, T A, Tinker, L E, Uitterlinden, A G, Van Setten, J, Voss, A, Waldenberger, M, Wilhelmsen, K C, Willemsen, G, Wong, Q, Zhang, Z M, Zonderman, A B, Cusi, D, Evans, M K, Greiser, K H, van der Harst, P, Hassan, M, Ingelsson, E, Järvelin, M-R, Kääb, S, Kähönen, M, Kivimaki, M, Kooperberg, C, Kuh, D, Lehtimäki, T, Lind, L, Nievergelt, C M, O'Donnell, C J, Oldehinkel, A J, Penninx, B W, Reiner, A P, Riese, H, Van Roon, A M, Rioux, J D, Rotter, J I, Sofer, T, Stricker, B H, Tiemeier, H, Vrijkotte, T G M, Asselbergs, F W, Brundel, B J J M, Heckbert, S R, Whitsel, E A, den Hoed, M, Snieder, H & de Geus, E J C 2017, 'Genetic loci associated with heart rate variability and their effects on cardiac disease risk', Nature Communications [E], vol. 8, 15805. https://doi.org/10.1038/ncomms15805