The Bayesian inference enabled us to compute the causal regulators of the differential connectivity in individual modules, defined as the genes controlling many downstream nodes in the respective network (see Extended Experimental Procedures). The causal regulators of the highest scoring immune/microglia module were rank-ordered based on the number of downstream nodes, i.e. the power of regulating other genes, as well as differential expression in LOAD brains. Here, we used a combined score as Gj=∏igji, where, gji is the discriminant value of a j in the case i, and is defined as (maxi(rji)+1−rji)∕∑jrji (Duda et al., 2000). In comparison to the average gene/node in a given network the causal regulators are expected to have a stronger effect on the clinical outcome as they direct the expression of a significant portion of the network module they reside in. The size of the gene membership for the different regional specific immune modules ranges from 386 in CB to 1108 in the PFC, with 247 of the genes in the CB detected in all regions (P=1e-19). The identity of the key causal regulators is
