MR Dictionary

InSIDE assumption (in two-sample MR using aggregate data)

The Instrument Strength Independent of Direct Effect (InSIDE) assumption a further assumption for MR-Egger and related MR methods (additional to core and additional IV assumptions outlined in Chapter 2). 

The assumption states that the association between the genetic instrument and exposure is not correlated with path from the genetic instrument to the outcome that is independent of the exposure of interest. If unbalanced pleiotropy is present and the InSIDE assumption is violated, then this is likely to result in a biased MR-Egger effect. Violation of the InSIDE assumption can occur if several genetic variants influence the outcome via the same pleiotropic path or if several variants are related to the same risk factor- outcome (unmeasured) confounder(s), as then the genetic instrument-exposure association is in part via that (those) confounders and it is also related to the outcome via the same confounder(s)

References

Other terms in 'Sources of bias and limitations in MR':