Comparison of Two Genome-Wide Association Studies for Heart Rate Response to Exercise from the UK Biobank

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 STrengthening of Reporting of Genetic Association 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 winners curse operating for a SNP from the Ramirez studys 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. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=183 HEIGHT=200 SRC="FIGDIR/small/21259806v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@134bf11org.highwire.dtl.DTLVardef@1ec23deorg.highwire.dtl.DTLVardef@26f712org.highwire.dtl.DTLVardef@26d148_HPS_FORMAT_FIGEXP M_FIG C_FIG