Bowden et al have shown that uncertainty in the associations between the genetic variants and the risk factor in univariable MR‐Egger can lead to attenuation towards the null when a causal effect exists between the risk factor and the outcome.34 This attenuation is approximately equal to the I 2 statistic from meta‐analysis of the weighted associations with the exposure β^Xjse(β^Yj)−1, with standard errors se(β^Xj)se(β^Yj)−1.34 Since the mean I 2 statistics for the simulation study in this paper were close to 100%, there was no substantial bias in the causal estimates due to uncertainty in the genetic associations for either the univariable or multivariable MR‐Egger methods. However, it is unclear whether uncertainty in the genetic associations with the risk factors would always lead to the attenuation of the causal estimates for the multivariable MR‐Egger method. Further research is required to investigate this.
