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

Nolte, Ilja M
Munoz, M Loretto
Tragante, Vinicius
Snieder, Harold
de Geus, Eco J C
CollaborationWith : Ehret, Georg Benedikt
Published in Nature Communications. 2017, vol. 8, p. 15805
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.
Keywords Blood PressureCohort StudiesEuropean Continental Ancestry Group/geneticsGenetic Predisposition to DiseaseGenome-Wide Association StudyHeart Diseases/genetics/physiopathologyHeart RateHumansHyperpolarization-Activated Cyclic Nucleotide-Gated Channels/geneticsMuscle Proteins/geneticsPolymorphismSingle NucleotidePotassium Channels/geneticsQuantitative Trait LociRGS Proteins/geneticsRisk Factors
PMID: 28613276
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Article (Published version) (533 Kb) - public document Free access
Research group Traits génétiques complexes (901)
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NOLTE, Ilja M et al. Genetic loci associated with heart rate variability and their effects on cardiac disease risk. In: Nature Communications, 2017, vol. 8, p. 15805. doi: 10.1038/ncomms15805 https://archive-ouverte.unige.ch/unige:127792

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Deposited on : 2019-12-11

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