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

(2017) Genetic loci associated with heart rate variability and their effects on cardiac disease risk. Nature Communications. ISSN 2041-1723

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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
Keywords: genome-wide association respiratory sinus arrhythmia parasympathetic regulation atrial-fibrillation metaanalysis mortality cohort recordings modulator pedigrees
Divisions: Other
Journal or Publication Title: Nature Communications
Journal Index: ISI
Volume: 8
Identification Number: Artn 15805 10.1038/Ncomms15805
ISSN: 2041-1723
Depositing User: مهندس مهدی شریفی
URI: http://eprints.mui.ac.ir/id/eprint/461

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