Functional Genomic Profiling of Schizophrenia-Associated Genes Reveals Key Microglial Regulators

However, the functional impact of SCZ-associated genes in microglia remains largely unexplored. Here, we performed an arrayed CRISPR targeting screen of 30 schizophrenia-associated genes predicted to be differentially expressed in human microglia-like cells.

Target genes were prioritized based on post-mortem transcriptomic relevance and predicted ontology-based roles in phagocytosis pathways. We quantified phagocytic activity and morphological changes following gene targeting using high-content confocal imaging. Key targets, including CYFIP1, MSR1, TREM2, SYK, ITGB2, ITGAM and IRF8, modulated phagocytosis and altered morphological properties consistent with activation states, validating their functional roles in microglia.