Re: “Multivariable Mendelian Randomization: The Use of Pleiotropic Genetic Variants to Estimate Causal Effects”

摘要

In the manuscript “Multivariable Mendelian Randomization: the Use of Pleiotropic Genetic Variants to Estimate Causal Effects” (1), we commented on an analysis method recently used in the literature (2), which we referred to as a “regression-based method.” We presented simulation results showing that the method had some weaknesses—in particular, not estimating the same parameter as that from a 2-stage least-squares analysis of individual-level data, and giving widely varying results when there were causal effects between the risk factors. A specific criticism of the method is that the uncertainty in the summarized associations (beta coefficients) used in the method is ignored.