Thirty loci identified for heart rate response to exercise and recovery implicate autonomic nervous system

Impaired capacity to increase heart rate (HR) during exercise (Delta HRex), and a reduced rate of recovery post-exercise (Delta HRrec) 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 Delta HRex and Delta HRrec in similar to 40,000 individuals, followed by replication in similar to 27,000 independent samples, all from UK Biobank. Six and seven single-nucleotide polymorphisms for Delta HRex and Delta HRrec, respectively, formally replicate. In a full data set GWAS, eight further loci for Delta HRex and nine for Delta HRrec are genome-wide significant (P <= 5 x 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.