The nature of AUD does not normally allow us to differentiate between pre-existing genetic differences and those due to the chronic alcohol consumption that is the hallmark of AUD. Some AUD-associated differences we observed (e.g., changes in inflammatory and myelinating processes) appear to be associated with the consequences of AUD. However, pre-existing genetic information (GWAS data and eQTL) allows us to identify possible causes of the disease and genes driving the effects we observed and inferred. We found several genes in multiple cell types with strong evidence of being linked to AUD. For example, the variant rs1412825, located within a locus positively associated with drinks per week,3 was negatively associated with expression of the gene Serine/threonine-protein phosphatase 2A regulatory subunit B" subunit gamma (PPP2R3C) in both oligodendrocytes and D1/D2 MSNs. This, combined with our finding that PPP2R3C had significantly lower expression in oligodendrocytes and D1/D2 MSNs in individuals with AUD, suggests that PPP2R3C could be protective against AUD. Interestingly, expression of PPP2R3C was recently shown to be significantly associated with PAU in the nucleus accumbens – another part of the
