Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator

Developments in genome-wide association studies and the increasing availability of summary genetic association data have made application of Mendelian randomization relatively straightforward. However, obtaining reliable results from a Mendelian randomization investigation remains problematic, as the conventional inverse-variance weighted method only gives consistent estimates if all of the genetic variants in the analysis are valid instrumental variables. We present a novel weighted median estimator for combining data on multiple genetic variants into a single causal estimate. This estimator is consistent even when up to 50% of the information comes from invalid instrumental variables. In a simulation…

• W
  Wellcome

  Award: 100114
• WT
  Wellcome Trust
• CR
  Cancer Research UK
• MR
  Medical Research Council

  Awards: MR/N501906/1, MC_UU_12013/1‐9, MR/L003120/1, MR/N501906/1, MC UU 12013/1