The co-expression network structure, its changes between non-demented and LOAD brains, and the genetic loci responsible for the expression co-variation behind these networks, collectively reflect molecular processes associated with LOAD. By linking the network modules to clinical outcome or LOAD neuropathology via a multiple regression analysis (Extended Experimental Procedures), we can infer key molecular processes associated with LOAD. A covariance matrix of the average expression correlation (∣r∣) between 49 modules, comprised of at least 100 probes, and 25 LOAD-related traits is shown in Figure 4A. We performed principal component analysis (PCA) to estimate the module-trait correlation and used the FDR method to assess the significance (see Extended Experimental Procedures). Of all modules, the immune/microglia showed correlation to the greatest number of LOAD-related neuropathology traits (Figure 4B). Expression of the PFC immune/microglia module correlated to atrophy levels in multiple brain regions, including frontal cortex (r=0.27, FDR=0.018), parietal (r=0.20, FDR=0.016), temporal (r=0.19, FDR=0.022) and neostriatum regions (r=0.28, FDR=3.3e-09) as well as ventricular enlargement (r=0.17, FDR=0.031). Several modules, however, showed correlation to a more restricted type of neuropathology, including the modules characteristic for
