Fig. 4: Mendelian randomization shows absence of linear and non-linear associations between genetically predicted RHR and all-cause mortality.

Linear and non-linear Mendelian randomization analyses were performed to test the association between genetically predicted RHR and all-cause mortality. a Forest plot of the linear MR analyses between genetically predicted RHR and all-cause mortality (Ncases = 16,289, Ncontrol = 396,183). With a single outcome, a two-sided P-value of P < 0.05 was considered significant. Hazard ratios and 95% confidence intervals are shown. The X-axis shows hazard ratio’s on a log₁₀ scale, the center as indicated by a gray line depicts a hazard ratio of 1. b Dose–response curve of the non-linear MR analyses between genetically predicted RHR and all-cause mortality (Ncases = 16,039, Ncontroles = 394,144). The comparisons are conducted within strata and therefore the graph provides information on the expected average change in the outcome if a person with an RHR of (say) 70 bpm instead had an RHR value of 90 bpm. The gradient at each point of the curve is the localized average causal effect. Shaded areas represent 95% confidence intervals. With a single outcome, a two-sided fractional polynomial non-linearity P-value of P < 0.05 was considered significant. The X-axis shows RHR, the Y-axis shows hazard ratios. The center as indicated by a dark gray line depicts a hazard ratio of 1. RHR resting heart rate, HR hazard ratio, CI confidence interval, MR Mendelian randomization, IVW inverse variance weighted, FE fixed effects, MRE multiplicative random effects.