Genetic study links components of the autonomous nervous system to heart-rate profile during exercise

Heart rate (HR) response to exercise, as defined by HR-increase upon exercise and HR-recovery after exercise, is an important predictor of mortality and believed to be modulated by the autonomic nervous system. However, the mechanistic basis underlying inter-individual differences remains to be elucidated. To investigate this, we performed a large-scale genome wide analysis of HR-increase and HR-recovery in 58,818 individuals. A total of 25 significant independent SNPs in 23 loci (P<8.3×10 −9 ) were associated with HR-increase or HR-recovery, and 36 candidate causal genes were prioritized that were enriched for pathways related to neuron biology. There was no evidence of a causal relationship with mortality or cardiovascular diseases, however, a nominal association with parental lifespan was observed (5.5×10 −4 ) that requires further study. In conclusion, our findings provide new biological and clinical insight into the mechanistic under-pinning of HR response to exercise, underscoring the role of the autonomous nervous system in HR-recovery. ABBREVIATIONS BMI Body mass index ECG Electrocardiography HR Heart rate HRR Heart rate recovery GWAS Genome-wide association study LD Linkage disequilibrium MAF Minor allele frequency SE Standard error CI Confidence interval