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

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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