Since the orientation of the genetic variants affects the interpretation of the direct effect, and the definition of the InSIDE assumption, the MR‐Egger intercept will vary between different orientations. In this example, the MR‐Egger intercept differed from zero when the variants were orientated with respect to HDL‐C and triglycerides, yet there was no evidence of directional pleiotropy or the InSIDE assumption being violated when the variants were orientated with respect to LDL‐C.
