Genetic Factors Control Heart Rate in Response to Exercise

MedicalResearch.com Interview with:

Professor Patricia Munroe PhD Professor of Molecular Medicine William Harvey Research Institute Barts and The London School of Medicine and Dentistry Queen Mary University of London

Prof. Munroe

Prof. Patricia Munroe PhD
Professor of Molecular Medicine
William Harvey Research Institute
Barts and The London School of Medicine and Dentistry
Queen Mary University of London

MedicalResearch.com: What is the background for this study?

Response: Over the years, it has become increasingly evident that impaired capacity to increase heart rate during exercise and reduce heart rate following exercise are important predictors of all-cause and cardiovascular mortality. A person’s capability to regulate their heart rate is the result of complex interactions of biological systems, including the autonomic nervous and hormonal systems. Prior work has demonstrated that genetic factors significantly contribute to variations in resting heart rate among different individuals, but less was known about the genetic factors modulating the response of heart rate to exercise and recovery.

MedicalResearch.com: What are the main findings? 

Response: We conducted genome-wide association studies (GWAS) for both heart rate response to exercise and recovery traits in ~40,000 individuals and followed up the top findings in a further ~27,000 independent individuals, all participants from the UK Biobank exercise stress test. In total, we discovered 30 loci, with eight loci being common to both traits. Bioinformatics analyses demonstrated that our identified genes were functionally involved in the neural development and the autonomic nervous system modulation. These findings support our hypothesis, impaired autonomic nervous system activity would reflect in a reduced response of heart rate to exercise and recovery.

MedicalResearch.com: What should readers take away from your report?

Response: Our findings advance our knowledge on key pathways controlling heart rate response to exercise and recovery, information which may be valuable in the future for cardiovascular risk prediction and may possibly guide the development of future therapeutic agents.  

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: We would like to expand our analyses to a larger sample size in order to discover further genes and additional biological pathways. Our current analyses including only  ~67,000 individuals is relatively small for a GWAS, so our findings only explained a small percent of the genetic contribution. Analysis of these traits in other ethnic groups would also be of interest. Finally, using functional assays to follow up on the candidate genes we have identified would improve our understanding of the physiology of heart rate modulation during exercise and recovery.

Citation:Julia Ramírez, Stefan van Duijvenboden, Ioanna Ntalla, Borbala Mifsud, Helen R Warren, Evan Tzanis, Michele Orini, Andrew Tinker, Pier D. Lambiase, Patricia B. Munroe. Thirty loci identified for heart rate response to exercise and recovery implicate autonomic nervous system. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-04148-1 

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