A comparison of robust Mendelian randomization methods using summary data

The number of Mendelian randomization (MR) analyses including large numbers of genetic variants is rapidly increasing. This is due to the proliferation of genome-wide association studies, and the desire to obtain more precise estimates of causal effects. Since it is unlikely that all genetic variants will be valid instrumental variables, several robust methods have been proposed. We compare nine robust methods for MR based on summary data that can be implemented using standard statistical software. Methods were compared in three ways: by reviewing their theoretical properties, in an extensive simulation study, and in an empirical example. In the simulation study, the best method, judged by mean squared error…

• WT
  Wellcome Trust

  Awards: 204623/Z/16/Z, 204623
• RS
  Royal Society

  Award: 204623/Z/16/Z
• VT
  Vereniging Trustfonds Erasmus Universiteit Rotterdam
• MR
  Medical Research Council