Testing and correcting for weak and pleiotropic instruments in two-sample multivariable Mendelian randomization.

ABSTRACT: Multivariable Mendelian randomization (MVMR) is a form of instrumental variable analysis which estimates the direct effect of multiple exposures on an outcome using genetic variants as instruments. Mendelian randomization and MVMR are frequently conducted using two-sample summary data where the association of the genetic variants with the exposures and outcome are obtained from separate samples. If the genetic variants are only weakly associated with the exposures either individually or conditionally, given the other exposures in the model, then standard inverse variance weighting will yield biased estimates for the effect of each exposure. Here, we develop a two-sample conditional F-statistic to test whether the genetic variants strongly predict each exposure conditional on the other expo

SUBMITTER: Sanderson E 

PROVIDER: S-EPMC9479726 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature