Chunk #16 — Results — Network analysis of gene expression of control and SZ hiPSC NPCs identifies perturbations in neuronal maturation and cellular adhesion
We used WGCNA to identify modules composed of highly co-expressed genes12 and found five gene modules (Figure 1b). Many of the gene modules identified in SZ hiPSC NPC GS predicted neuronal deficits (neuron differentiation, neuronal migration, glutamate receptor signaling and synaptic vesicle function), suggesting that neural deficits in SZ might be specified before neural differentiation. We validated 8/12 neuronal migration-associated candidate genes by qPCR across an increased number of individuals (six controls and four SZ patients) and NPC lines (two NPC lines per SZ patient; ⩾1.3-fold changes in expression; P<0.01) (Figure 1c and Supplementary Table 4). We performed gene ontology analysis using manually curated databases; in addition to neurophysiological pathways involving synapse formation and synaptic transmission, our analysis also identified significant perturbations of cellular adhesion genes, (Supplementary Figures 4A and B, and 5D).
