In this study, we conducted a 7-day exposure to ethanol, and thus, we could not assess the effects of long-term heavy drinking in the high PRS or low PRS group. In addition, the subjects’ cells were reprogrammed. The experimental system we used exposed newly generated and naive microglia with different genetic backgrounds to “toxic” concentrations of ethanol (but not long term). Although the high AUD PRS subjects were diagnosed with AUD, and the low PRS subjects were not, our study likely could not provide insight into whether a prior history of alcohol drinking interacts with PRS to affect the microglial phenotype in vitro after ethanol exposure. Therefore, we focused on the a priori genetic risk factors and observed changes in gene expression in high PRS microglia, indicating a neuroimmune response. These same changes in microglia may occur in individuals at risk with long-term heavy drinking, but further studies are needed to assess this possibility.
