The value of the intercept term β^0E can be interpreted as an estimate of the average pleiotropic effect across the genetic variants (Bowden et al., 2015). The pleiotropic effect is the effect of the genetic variant on the outcome that is not mediated via the exposure. An intercept term that differs from zero is indicative of overall directional pleiotropy; that is, pleiotropic effects do not cancel out and the IVW estimate is biased.
