Figure 3. Causal mediation analysis of plasma protein effects on neurological and psychiatric diseases through IDPs using multivariable Mendelian randomization.

Plots display the estimated total, direct, and IDP-mediated effects of plasma proteins on disease risk. (a) Weighted median (WM) based MVMR results, showing robust estimates of the total protein effects along with direct and IDP-mediated effects. (b) Inverse-variance weighted (IVW) MVMR results for the same protein-disease pairs. In both panels, the mediated effect represents the proportion of the protein-disease association attributable to variation in the IDP, whereas the direct effect captures the remaining association after accounting for mediation.