In Scenario 2 (directional pleiotropy, InSIDE assumption satisfied), estimates from the IVW method are biased with inflated Type 1 error rates. Estimates from the weighted median methods are less biased, although there is a consistent bias in the direction of the pleiotropic variants. Nominal Type 1 error rates are maintained when only 10% of genetic variants are invalid IVs, although Type 1 error rates are above the expected 5% rate when 20% or more genetic variants are invalid IVs. However, even though they are inflated, Type 1 error rates are far lower for the median‐based methods than those from the IVW method. The penalized weighted median estimates are less biased when a few genetic variants are invalid, but when 30% of genetic variants are invalid, it seems that the invalid IVs are often retained in the analysis (as their estimates are homogeneous with each other) and valid IVs are excluded. Estimates from MR‐Egger regression are close to unbiased, and Type 1 error rates are at nominal levels, suggesting its utility as a sensitivity analysis method when the InSIDE assumption is
