In astrocytes, six transcription factors were implicated in regulating AUD-associated differences in both expression and chromatin accessibility, including the gene JUND (JunD proto-oncogene), which had increased regulatory activity in individuals with AUD in astrocytes (Extended Data Fig. 8). We found 142 transcription factor motifs with significantly higher enrichment in those with AUD (p < 0.05) using chromVAR.52 15 of the top 20 enriched motifs (by p-value) with significantly higher activity in cells from individuals with AUD are annotated by JASPAR53 as being associated with bZIP transcription factors (p <= 0.005; Supplementary Table 16). The bZIP transcription factor motif for JUND had significantly higher enrichment in astrocytes in individuals with AUD (p = 0.01, Fig. 6D-E). Astrocytes with high JUND motif enrichment were largely in regions with high complement component 3 (C3) expression, a marker of reactive astrogliosis.54 There was higher expression of C3 in individuals with AUD (1.65 fold, padj = 0.0007; Fig. 6F).
