In the second scenario, where there is a lack of biological evidence to suggest a multivariable framework, univariable IVW would generally be considered as the primary analysis method and univariable MR‐Egger as the main sensitivity analysis. However, if the genetic variants are associated with other risk factors, multivariable MR‐Egger could also be used as a sensitivity analysis as its assumptions are more likely to be satisfied and it may have greater power to detect a causal effect than univariable MR‐Egger. An example of the use of multivariable MR as a sensitivity analysis is an MR study on plasma urate concentrations and CHD risk.29 To account for measured and unmeasured pleiotropic associations of the genetic variants, the authors performed the multivariable IVW and univariable MR‐Egger methods as sensitivity analyses. This investigation may have benefited from performing the multivariable MR‐Egger method to simultaneously account for both measured and unmeasured pleiotropic associations.
