In conclusion, the approaches of this paper should not be interpreted as a pretext for conducting Mendelian randomization analyses with large numbers of genetic variants without prior regard to the validity of the IV assumptions. However, they provide simple graphical and statistical methods that can detect some violations of the IV assumptions, and can therefore can used as a sensitivity analysis for assessing whether the effect estimation in a Mendelian randomization analysis is influenced by directional pleiotropic effects of the genetic variants.