Thirty loci identified for heart rate response to exercise and recovery implicate autonomic nervous system
Impaired capacity to increase heart rate (HR) during exercise (ΔHRex), and a reduced rate of recovery post-exercise (ΔHRrec) are associated with higher cardiovascular mortality rates. Currently, the genetic basis of both phenotypes remains to be elucidated. We conduct genome-wide association studies (GWASs) for ΔHRex and ΔHRrec in ~40,000 individuals, followed by replication in ~27,000 independent samples, all from UK Biobank. Six and seven single-nucleotide polymorphisms for ΔHRex and ΔHRrec, respectively, formally replicate. In a full data set GWAS, eight further loci for ΔHRex and nine for ΔHRrec are genome-wide significant (P ≤ 5 × 10-8). In total, 30 loci are discovered, 8 being common across traits. Processes of neural development and modulation of adrenergic activity by the autonomic nervous system are enriched in these results. Our findings reinforce current understanding of HR response to exercise and recovery and could guide future studies evaluating its contribution to cardiovascular risk prediction. ; This research has been conducted using the UK Biobank Resource (application 8256—Understanding genetic influences in the response of the cardiac electrical system to exercise) and is supported by Medical Research Council grant MR/N025083/1. We also wish to acknowledge the support of the NIHR Cardiovascular Biomedical Research Centre at Barts and Queen Mary University of London, UK. J.R. acknowledges support from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 608765. P.D.L. acknowledges support from the UCLH Biomedicine NIHR, Barts Heart Centre BRC. M.O. is supported by an IEF 2013 Marie Curie fellowship. B.M. holds an MRC eMedLab Medical Bioinformatics Career Development Fellowship, funded from award MR/L016311/1. This project was enabled through access to the MRC eMedLab Medical Bioinformatics infrastructure, award MR/L016311/1.