Key result
A systematic review of two large genome-wide association studies from the UK Biobank demonstrated good agreement between their polygenic risk scores for heart rate response to exercise, despite differences in identified SNPs and methodologies.
Why the study?
Heart rate changes during and after exercise are associated with cardiovascular mortality, prompting a systematic review of genome-wide association studies with over 10,000 participants to compare Polygenic Risk Scores across studies.
Systematic Review
This systematic review highlights that despite methodological differences between two large GWAS on the UK Biobank, there is good agreement in polygenic risk scores for heart rate response to exercise, though non-European ancestries remain underrepresented.
Supports reproducibility of polygenic scores for exercise heart rate response; leaves clinical utility open pending prospective validation.
The short-term changes in heart rate (HR) during and after exercise are important physiologic traits mediated via the autonomic nervous system. Variations in these traits are associated with mortality from cardiovascular causes. We conducted a systematic review of genome-wide association studies for these traits (with >10,000 participants) with the aim of comparing Polygenic Risk Scores (PRS) from different studies. Additionally, we applied the ST rengthening of R eporting of G enetic A ssociation Studies (STREGA) statement for assessing the completeness of reporting of evidence. Our systematic search yielded two studies (Verweij et al. and Ramirez et al.) that met our inclusion criteria. Both were conducted on the UK Biobank. Both defined their exercise traits as the difference between resting HR and the maximum HR during exercise. Their recovery traits were defined differently. Verweij et al. defined 5 recovery traits as the differences between the peak HR during exercise and the HRs at 10-50 sec post exercise cessation. Ramirez et al. defined their recovery trait as the difference between peak HR during exercise and the minimum HR during the minute post exercise cessation. While Ramirez et al. divided their sample into discovery and replication subsets, Verweij et al. analyzed the whole sample together. In terms of results, there were several common SNPs identified between studies and traits. There was evidence for the phenomenon of winner’s curse operating for a SNP from the Ramirez study’s HR recovery analysis. Many of the SNPs were mutually exclusive between the studies. However, there was a good agreement of PRS from the studies. The differences in the results could be attributed to the different exclusion criteria, analytic approaches, and definitions of traits used. Both studies had an under-representation of individuals of non-European ancestry compared to those of European ancestry. Further studies with proportionate representation of individuals of all ancestries would help address this gap.
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Thakral et al. (2021) conducted a systematic review in Heart rate response to exercise and recovery. Genetic variants (SNPs) associated with heart rate response was evaluated on Agreement of Polygenic Risk Scores (PRS) and identified SNPs between studies. A systematic review of two large genome-wide association studies from the UK Biobank demonstrated good agreement between their polygenic risk scores for heart rate response to exercise, despite differences in identified SNPs and methodologies.
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