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

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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 et al (show 154 more authors) , van Dongen, Jenny, Gogarten, Stephanie M, Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P, Kumar, Jitender, van der Laan, Sander W, Lyytikainen, Leo-Pekka, Maihofer, Adam X, Minassian, Arpi, van der Most, Peter J, Mueller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D, Thayer, Julian F, Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G, de Bakker, Paul IW, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J, Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R, Christophersen, Ingrid E, Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F, Floras, John S, Franco, Oscar H, Friberg, Peter, Gademan, Maaike GJ, Geyer, Mark A, Giedraitis, Vilmantas, Hartman, Catharina A, Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kahonen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M, Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C, Lefrandt, Joop D, Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C, Lin, Henry J, Lindgren, Cecilia M, Lubitz, Steven A, Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P, Nalls, Mike A, Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E, O'Connor, Daniel T, Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M, Raitakari, Olli T, Risbrough, Victoria B, Sinner, Moritz F, Siscovick, David, Smit, Johannes H, Smith, Nicholas L, Soliman, Elsayed Z, Sotoodehnia, Nona, Staessen, Jan A, Stein, Phyllis K, Stilp, Adrienne M, Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundstrom, Johan, Swenne, Cees A, Syvanen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D, Teumer, Alexander, Thornton, Timothy A, Tinker, Lesley E, Uitterlinden, Andre G, van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C, Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B, Cusi, Daniele, Evans, Michele K, Greiser, Halina K, van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Jarvelin, Marjo-Riitta, Kaab, Stefan, Kahonen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimaki, Terho, Lind, Lars, Nievergelt, Caroline M, O'Donnell, Chris J, Oldehinkel, Albertine J, Penninx, Brenda, Reiner, Alexander P, Riese, Harriette, van Roon, Arie M, Rioux, John D, Rotter, Jerome I, Sofer, Tamar, Stricker, Bruno H, Tiemeier, Henning, Vrijkotte, Tanja GM, Asselbergs, Folkert W, Brundel, Bianca JJM, Heckbert, Susan R, Whitsel, Eric A, den Hoed, Marcel, Snieder, Harold and de Geus, Eco JC (2017) Genetic loci associated with heart rate variability and their effects on cardiac disease risk. NATURE COMMUNICATIONS, 8 (1). 15805-.

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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.

Item Type:	Article
Uncontrolled Keywords:	Humans, Heart Diseases, Genetic Predisposition to Disease, RGS Proteins, Potassium Channels, Muscle Proteins, Risk Factors, Cohort Studies, Blood Pressure, Heart Rate, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, White People
Depositing User:	Symplectic Admin
Date Deposited:	26 Jun 2017 10:51
Last Modified:	13 Feb 2023 23:16
DOI:	10.1038/ncomms15805
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3008110