Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders

Nat Genet. 2013 Jun;45(6):621-31. doi: 10.1038/ng.2610. Epub 2013 Apr 14.

Abstract

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.

Publication types

  • Meta-Analysis

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / genetics*
  • Arrhythmias, Cardiac / physiopathology
  • Gene Frequency
  • Genetic Loci
  • Genome-Wide Association Study
  • Heart Conduction System / physiopathology
  • Heart Rate / genetics*
  • Humans
  • Metabolic Networks and Pathways
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci

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