Increased NRG1 expression has been observed in postmortem SCZD brain tissue13. NRG1 expression was increased in SCZD hiPSC neurons (Fig. 4D–F) but not SCZD fibroblasts (HF), hiPSCs or NPCs (Fig. 4E), demonstrating the importance of studying gene expression changes in the cell type relevant to disease. In all, 596 unique genes (271 upregulated and 325 downregulated) showed greater than 1.30-fold-expression changes between SCZD and control hiPSC neurons (p<0.05) (SI Fig. 11A,B; SI Table 3). Of these genes, 13% (74) have published associations with SCZD and 16% (96) have been linked to SCZD by postmortem gene expression profiles available through the Stanley Medical Research Institute14 (SI Table 3); in total 25% (149) of our differentially expressed genes have been previously implicated in SCZD. Gene ontology (GO) analysis identified significant perturbations of glutamate, cAMP and WNT signaling (Fig. 4A–C; SI Table 4; SI Fig. 11C), pathways required for activity-dependent refinement of synaptic connections and long-term potentiation15–17. Sixteen of 17 candidate genes from these families were validated by qPCR (SI Table 2; Fig. 4F; SI Fig. 11E).
