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

Julia Ramírez; Stefan van Duijvenboden; Ioanna Ntalla; Borbala Mifsud; Helen R Warren; Evan Tzanis; Michele Orini; Andrew Tinker; Pier D Lambiase; Patricia B Munroe

doi:10.1038/s41467-018-04148-1

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

Nat Commun. 2018 May 16;9(1):1947. doi: 10.1038/s41467-018-04148-1.

Authors

Julia Ramírez^{1

2}, Stefan van Duijvenboden^{1

2}, Ioanna Ntalla¹, Borbala Mifsud^{1

3}, Helen R Warren^{1

3}, Evan Tzanis^{1

3}, Michele Orini^{4

5}, Andrew Tinker^{1

3}, Pier D Lambiase^{6

7}, Patricia B Munroe^{8

9}

Affiliations

¹ Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
² Institute of Cardiovascular Science, University College London, London, WC1E 6BT, UK.
³ NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
⁴ Barts Heart Centre, St Bartholomews Hospital, London, EC1A 7BE, UK.
⁵ Mechanical Engineering Department, University College London, London, WC1E 6BT, UK.
⁶ Institute of Cardiovascular Science, University College London, London, WC1E 6BT, UK. p.lambiase@ucl.ac.uk.
⁷ Barts Heart Centre, St Bartholomews Hospital, London, EC1A 7BE, UK. p.lambiase@ucl.ac.uk.
⁸ Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK. p.b.munroe@qmul.ac.uk.
⁹ NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK. p.b.munroe@qmul.ac.uk.

Abstract

Impaired capacity to increase heart rate (HR) during exercise (ΔHR^ex), and a reduced rate of recovery post-exercise (ΔHR^rec) 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 ΔHR^ex and ΔHR^rec in ~40,000 individuals, followed by replication in ~27,000 independent samples, all from UK Biobank. Six and seven single-nucleotide polymorphisms for ΔHR^ex and ΔHR^rec, respectively, formally replicate. In a full data set GWAS, eight further loci for ΔHR^ex and nine for ΔHR^rec 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autonomic Nervous System / metabolism*
Autonomic Nervous System / physiopathology
Cardiovascular Diseases / genetics*
Cardiovascular Diseases / physiopathology
Exercise*
Female
Genetic Predisposition to Disease / genetics*
Genome-Wide Association Study / methods
Heart Rate / genetics*
Heart Rate / physiology
Humans
Male
Polymorphism, Single Nucleotide
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding