IVW estimate is pulled away from the true value by the invalid instruments, which yield biased estimates of the causal effect. Figure 2 (right) shows the same scatter plot for an infinite sample size. Now the six valid instruments lie perfectly on the true line, and all yield the same true causal estimate. The median ratio estimate (in this case, an average of the fifth and sixth ratio estimates) is the true causal effect. In contrast, the IVW estimate remains biased even with infinite data, as the ratio estimate from each genetic variant always contributes toward the overall IVW estimate.
