Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
SourceNature Genetics, 45, 6, (2013), pp. 621-631
Article / Letter to editor
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Epidemiology, Biostatistics & HTA
SubjectIGMD 5: Health aging / healthy living NCEBP 14: Cardiovascular diseases; NCEBP 1: Molecular epidemiology ONCOL 5: Aetiology, screening and detection; ONCOL 5: Aetiology, screening and detection
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.
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