Combining information on multiple instrumental variables in Mendelian randomization: comparison of allele score and summarized data methods

Mendelian randomization is the use of genetic instrumental variables to obtain causal inferences from observational data. Two recent developments for combining information on multiple uncorrelated instrumental variables (IVs) into a single causal estimate are as follows: (i) allele scores, in which individual-level data on the IVs are aggregated into a univariate score, which is used as a single IV, and (ii) a summary statistic method, in which causal estimates calculated from each IV using summarized data are combined in an inverse-variance weighted meta-analysis. To avoid bias from weak instruments, unweighted and externally weighted allele scores have been recommended. Here, we propose equivalent approaches…

• W
  Wellcome

  Award: 100114
• WT
  Wellcome Trust
• BH
  British Heart Foundation

  Award: CH/12/2/29428
• MR
  Medical Research Council

  Awards: K006215, MR/L003120/1, MR/K006215/1