To determine which transcription factors and their target genes become more or less active in individuals with AUD, we used LINGER40, a recently developed tool for inferring gene regulatory networks from paired single-cell expression and chromatin accessibility data (see “Methods”). We used the same pseudobulk expression and accessibility data used in the differential analyses above to construct the regulatory network and extracted key transcription factor-target gene subnetworks (modules) within it (Supplementary Data 14). Several regulatory modules were significantly enriched for genes from the two large-scale alcohol-related GWAS4,6. Modules 1, 2, 3, and 10 were enriched for genes associated with PAU, and modules 3 and 8 were enriched for genes associated with drinks per week (Supplementary Fig. 7a).
