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

Journal article
Authors I. M. Nolte
M. L. Munoz
V. Tragante
A. T. Amare
R. Jansen
A. Vaez
B. von der Heyde
C. L. Avery
J. C. Bis
B. Dierckx
J. van Dongen
S. M. Gogarten
P. Goyette
J. Hernesniemi
V. Huikari
S. J. Hwang
D. Jaju
K. F. Kerr
A. Kluttig
B. P. Krijthe
J. Kumar
S. W. van der Laan
L. P. Lyytikainen
A. X. Maihofer
A. Minassian
P. J. van der Most
M. Muller-Nurasyid
M. Nivard
E. Salvi
J. D. Stewart
J. F. Thayer
N. Verweij
A. Wong
D. Zabaneh
M. H. Zafarmand
A. Abdellaoui
S. Albarwani
C. Albert
A. Alonso
F. Ashar
J. Auvinen
T. Axelsson
D. G. Baker
P. I. W. de Bakker
M. Barcella
R. Bayoumi
R. J. Bieringa
D. Boomsma
G. Boucher
A. R. Britton
I. E. Christophersen
A. Dietrich
G. B. Ehret
P. T. Ellinor
M. Eskola
J. F. Felix
J. S. Floras
O. H. Franco
Peter Friberg
M. G. J. Gademan
M. A. Geyer
V. Giedraitis
C. A. Hartman
D. Hemerich
A. Hofman
J. J. Hottenga
H. Huikuri
N. Hutri-Kahonen
F. Ashar
F. Ashar
M. Juonala
A. M. Kiviniemi
J. A. Kors
M. Kumari
T. Kuznetsova
C. C. Laurie
J. D. Lefrandt
Y. Li
Y. Li
D. P. Liao
M. C. Limacher
H. J. Lin
C. M. Lindgren
S. A. Lubitz
A. Mahajan
B. McKnight
H. M. zu Schwabedissen
Y. Milaneschi
N. Mononen
A. P. Morris
M. A. Nalls
G. Navis
M. Neijts
K. Nikus
K. E. North
D. T. O'Connor
J. Ormel
S. Perz
A. Peters
B. M. Psaty
O. T. Raitakari
V. B. Risbrough
M. F. Sinner
D. Siscovick
J. H. Smit
N. L. Smith
E. Z. Soliman
N. Sotoodehnia
J. A. Staessen
P. K. Stein
A. M. Stilp
K. Stolarz-Skrzypek
K. Strauch
J. Sundstrom
C. A. Swenne
A. C. Syvanen
J. C. Tardif
K. D. Taylor
A. Teumer
T. A. Thornton
L. E. Tinker
A. G. Uitterlinden
J. van Setten
A. Voss
M. Waldenberger
K. C. Wilhelmsen
G. Willemsen
Q. N. Wong
Z. M. Zhang
A. B. Zonderman
D. Cusi
M. K. Evans
H. K. Greiser
P. van der Harst
M. Hassan
E. Ingelsson
M. R. Jarvelin
S. Kaab
M. Kahonen
M. Kivimaki
C. Kooperberg
D. Kuh
T. Lehtimaki
L. Lind
C. M. Nievergelt
C. J. O'Donnell
A. J. Oldehinkel
B. Penninx
A. P. Reiner
H. Riese
A. M. van Roon
J. D. Rioux
J. I. Rotter
T. Sofer
B. H. Stricker
H. Tiemeier
T. G. M. Vrijkotte
F. W. Asselbergs
Bjjm Brundel
S. R. Heckbert
E. A. Whitsel
M. den Hoed
H. Snieder
E. J. C. de Geus
Published in Nature Communications
Volume 8
ISSN 2041-1723
Publication year 2017
Published at Institute of Medicine, Department of Molecular and Clinical Medicine
Language en
Keywords genome-wide association, respiratory sinus arrhythmia, parasympathetic, regulation, atrial-fibrillation, metaanalysis, mortality, cohort, recordings, modulator, pedigrees, Science & Technology - Other Topics, hwartz pj, 1992, circulationsymp on current perspectives on the problem of sudden cardiac death, sep 24-25, 1990, dallas, tx, v85, p77
Subject categories Cardiac and Cardiovascular Systems


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.

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