We used data from UK Biobank for replication of the selected SNVs (at the time of analysis genetic data were available for 150 000 individuals). The UK Biobank data were analysed with untransformed HR as the phenotype, with no exclusions for medication use. In UK Biobank resting HR was assessed by two methods: first, pulse rate using an automated reading during blood pressure measurement, and second, pulse rate during arterial stiffness measurement using the pulse wave form obtained of the finger with an infra red sensor. When multiple HR measurements were available during the first visit for an individual, these measurements were averaged. In 99.7% of participants at least one single measurement was available. Individuals were excluded with extreme (> 4 SD) values (N = 818). Further details are provided (17). The results of our European exome discovery meta-analysis for RR were combined with the UK Biobank replication results for HR (N = 134 251), and a combined meta-analysis, using sample-size weighted fixed effects meta-analysis in METAL was performed (33). All alleles were aligned between the discovery and replication data,
