To determine which transcription factors and their target genes become more or less active in individuals with AUD, we used LINGER,43 a recently developed tool for inferring gene regulatory networks from paired single-cell expression and chromatin accessibility data (see Online Methods). We pooled the pseudobulk data tested for differential accessibility across all cell types to construct the regulatory network. From this network, we extracted key transcription factor-target gene subnetworks (modules). Several regulatory modules were significantly enriched for genes from the two GWAS studies utilized in our analyses. Modules 1, 2, 3, and 10 were enriched for genes associated with PAU,5 and modules 3 and 8 were enriched for genes associated with drinks per week3 (Fig. 6A).
