Gene set enrichment analysis using pathways from the Reactome database39 showed that genes that differ in expression with respect to AUD were enriched in hundreds of pathways in many cell types (Fig. 2c, Supplementary Data 9). Successive hierarchical and manual grouping of pathways revealed that many immune response pathways—such as the adaptive immune system, innate immune system, and cytokine signaling in the immune system—were enriched in multiple cell types from individuals with AUD. In individuals with AUD, DEGs in oligodendrocytes were enriched for several pathways associated with synaptic regulation and depolarization, such as Neurotransmitter Receptors and Postsynaptic Signal Transmission and Voltage Gated Potassium Channels. D1/D2 and FS neurons had decreases in gene expression within pathways related to translation and metabolism, notably different than the canonical D1 and D2 MSN clusters, which had increases in gene expression mostly in immune-related pathways.
