The mediational model for EPs depicted in Figure 1b assumes that all the genetic risk factor for PD operates through EP. This model may be less realistic than the partial mediational one depicted in Figure 3. In this partial mediation model, some of the genetic effect on PD is mediated through EP but some bypasses EP to have a direct impact on PD. This scenario would provide another possible explanation for the not uncommon observation that the genetic influence on EP (be it an odds ratio in an association design or heritability from a twin study) is less than that on PD. For the present, ignoring problems of reliability of measurement, we can see from Figure 3 that the genetic signal for EP will exceed that for PD only when aEP > (aPD+aEPβ+2aPDaEPβ).
