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Chunk #9 — RESULTS — Differential transcriptomic profiles between high-PRS and low-PRS microglial cells

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Polygenic risk for alcohol use disorder affects cellular responses to ethanol exposure in a human microglial cell model.
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We identified 1980 differentially expressed genes (DEGs) between high-PRS and low-PRS microglial cells in the absence of ethanol (Fig. 2A). Among these DEGs, the genes with higher expression (n = 1013) in AUD high-PRS showed notable enrichment of Gene Ontology (GO) biological process terms related to chromosome separation regulation and mitotic sister chromatid separation (Fig. 2B). In addition, these genes were significantly enriched for receptor activator (Fig. 2C) and cellular component ontologies relating to chromosomes and centromeric regions (Fig. 2D). On the other hand, the genes with lower expression (n = 967) in AUD high-PRS exhibited enrichment in biological functions related to immune signaling, specifically involving peptide antigen assembly with the MHCII protein complex and antigen processing and presentation (Fig. 2B). In terms of molecular function, these lower DEGs were predominantly linked to immune receptor activity, antigen binding, and MHCII protein complex binding (Fig. 2C), with their cellular component enrichment observed in the MHCII protein complex (Fig. 2D). Notably, a higher expression level of “chromosome separation” genes in the high-PRS microglial cells was observed when compared with low-PRS microglial cells