In this study, subject-specific microglia were generated from iPSC lines derived from selected participants with high AUD PRS (high-PRS, n = 8, top 75 percentile, five males, three females, all diagnosed with AUD) or low AUD PRS (low-PRS, n = 10, bottom 25 percentile, five males and five females, all unaffected). These individuals were from the Collaborative Study on the Genetics of Alcoholism (COGA). COGA has found many genetic and molecular mechanisms underlying the functional alteration in AUD (41). We selected subjects with a defined clinical diagnosis of AUD with high-PRS or control samples with low-PRS with no AUD (12), which provide a unique opportunity to investigate the gene and environment (i.e., ethanol exposure) interaction and cellular functions. Because PRS summarizes a large number of genomic variations, and there are no consistent variants defining each group, we expected to find 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
