To determine the AUD-associated differences in chromatin accessibility for each cell type, we calculated the differentially accessible chromatin regions (DARs) – i.e., open chromatin regions that differed in accessibility between individuals with AUD and those without, again using a pseudobulk method. Samples were removed on a cell type-specific basis if the sample contained less than 50 cells of that cell type (See Supplementary Table 12 for a summary of the number of pseudobulk samples created for each cell type). We identified DARs for eight cell types (Supplementary Table 12); of those, only oligodendrocytes, astrocytes, D1 neurons, and D2 neurons had over 50 DARs (padj < 0.2; Fig. 4C). Just as with the DEGs, most of the differences were in the positive direction – chromatin was on average more open in samples from individuals with AUD. However, most of these chromatin accessibility differences were relatively small – only in oligodendrocytes did any DARs surpass an absolute log2 fold change of 0.5.
