a large degree of variability among cell lines within each group. In highly enriched human microglial cells derived from iPSCs, we found that ethanol exposure leads to up-regulation of CD68 expression and alterations in microglial morphology, with distinct effects observed in microglia derived from subjects with different AUD PRS. Transcriptomic analysis unveiled differences between high-PRS and low-PRS microglial cells in the expression of genes related to the major histocompatibility complex (MHC) II complex and to phagocytosis after ethanol exposure. Furthermore, an enhanced phagocytic process with increased CLEC7A (C-type lectin domain family 7 member A) RNA expression was observed in high-PRS microglial cells following ethanol exposure, which was not observed in low-PRS microglial cells. Our study reveals the intricate interplay between AUD-related polygenetic factors and microglial function in AUD, offering important insights into the mechanism underlying AUD in humans.
