Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

Additional Metadata
Persistent URL dx.doi.org/10.1038/ng.2610, hdl.handle.net/1765/57453
Journal Nature Genetics
Citation
den Hoed, M, Eijgelsheim, M, Esko, T, Brundel, B.J.J.M, Peal, D.S, Evans, D.M, … Loos, R.J.F. (2013). Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nature Genetics, 45(6), 621–631. doi:10.1038/ng.2610