AUD is a complex genetic disorder, and although most individual genetic variants do not have genome-wide notable effects when considered collectively in a PRS, they quantify part of an individual’s susceptibility to developing the disorder (63–65). We investigated how the polygenic background, represented as PRS, affects microglial function; how intermittent exposure to ethanol affects microglial function; and how the two factors interact. It is likely that many of the genetic variants summarized in PRS can be predicted to affect gene regulatory networks either directly or indirectly. In the absence of ethanol, we found significant DEGs when comparing microglia from individuals with AUD and a high PRS for AUD (i.e., high-PRS) to those from individuals without AUD and with low PRS (i.e, low-PRS). The genes more highly expressed in high-PRS microglial cells were enriched in pathways related to receptor activation and chromosome separation, while those expressed at lower levels were enriched in genes related to immune signaling, particularly with the MHCII complex.
