Best (but oft-forgotten) practices: the design, analysis, and interpretation of Mendelian randomization studies

Mendelian randomization (MR) is an increasingly important tool for appraising causality in observational epidemiology. The technique exploits the principle that genotypes are not generally susceptible to reverse causation bias and confounding, reflecting their fixed nature and Mendel’s first and second laws of inheritance. The approach is, however, subject to important limitations and assumptions that, if unaddressed or compounded by poor study design, can lead to erroneous conclusions. Nevertheless, the advent of 2-sample approaches (in which exposure and outcome are measured in separate samples) and the increasing availability of open-access data from large consortia of genome-wide association studies and…

• CR
  Cancer Research UK

  Award: C52724/A20138
• MR
  Medical Research Council

  Awards: MC_EX_MR/L012286/1, MR/N501906/1, MR/L003120/1, MC_UU_00002/3