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However, the functional impact of SCZ-associated genes in microglia remains largely unexplored. Here, we performed an arrayed CRISPR targeting screen of 30 SCZ-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\n                    <jats:italic>CYFIP1, MSR1, TREM2, SYK, ITGB2<\/jats:italic>\n                    ,\n                    <jats:italic>ITGAM<\/jats:italic>\n                    , and\n                    <jats:italic>IRF8<\/jats:italic>\n                    , modulated phagocytosis and altered morphological properties consistent with activation states, validating their functional roles in microglia. To elucidate transcriptional impact, we further applied a multiplexed RNA sequencing platform across gene targets. These analyses revealed gene-specific transcriptional signatures, implicating divergent pathways related to phagocytic, activation, cytoskeletal, and lysosomal function. Together, these findings demonstrate the utility of CRISPR-based functional genomics in characterizing microglia function and identifying new target genes and mechanisms that may underlie their contributions to SCZ pathophysiology.\n                  <\/jats:p>","DOI":"10.1038\/s41386-026-02406-1","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T10:41:10Z","timestamp":1776336070000},"page":"1718-1727","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Functional genomic profiling of schizophrenia-associated genes reveals key microglial regulators"],"prefix":"10.1038","volume":"51","author":[{"given":"Joy E.","family":"Horng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam T.","family":"McCrea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca E.","family":"Batorsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua J.","family":"Bowen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Boschian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoonjae","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5862-6757","authenticated-orcid":false,"given":"Roy H.","family":"Perlis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1045-1158","authenticated-orcid":false,"given":"Steven D.","family":"Sheridan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"2406_CR1","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1016\/j.tics.2015.09.009","volume":"19","author":"TD Cannon","year":"2015","unstructured":"Cannon TD. 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