We developed and applied an integrative network-based approach to identify modules of genes associated with neurodegenerative disease (Figure 1A-C). We processed 1647 autopsied tissues from dorsolateral prefrontal cortex (PFC), visual cortex (VC) and cerebellum (CB) in 549 brains of 376 LOAD patients and 173 non-demented healthy controls (Figure 1A). All subjects were diagnosed at intake and each brain underwent extensive LOAD-related pathology examination. We note that the known APOE genotype exposure was confirmed in the HBTRC sample, showing an odds ratio of 3.74 per copy ε4 allele (P=4.1e-13). Each tissue sample was profiled for 39,579 transcripts representing 25,242 known and 14,337 predicted gene expression traits and each subject genotyped for 838,958 unique SNPs (Figure 1A). Unless otherwise noted, gene expression analyses were adjusted for age and sex, postmortem interval (PMI) in hours, sample pH and RNA integrity number (RIN). In the overall cohort of LOAD and non-demented brains the mean±SD for sample PMI, pH and RIN were 17.8±8.3, 6.4±0.3 and 6.8±0.8, respectively. Extensive analysis of the effect of covariates on gene expression variation in LOAD and non-demented brains was carried
