The multivariable models have assumed that the risk factors do not have causal effects on each other. The additional simulation study has illustrated that the multivariable MR‐Egger method estimates the direct causal effects of the risk factors on the outcome, irrespective of whether the risk factors are causally related. There was, however, a reduction in precision and power to detect the causal effect for multivariable MR‐Egger when a causal relationship between the risk factors was present. Conversely, univariable MR‐Egger will produce consistent causal estimates of the total effect if the InSIDE assumption for univariable MR‐Egger is satisfied.
