We identified cis and trans driver TFs underlying epigenetic and transcriptome changes between individuals with and without AUD using a linear regression model, Y=Aβ+β0+ε. For transcriptome drivers, the regression model predicted the log transformation of the gene expression fold change between individuals with and without AUD (Y) from cell type-specific TF-TG trans-regulation (A). For epigenetic drivers, the model predicted chromatin accessibility changes (Y) from the cell type-specific TF-regulatory element cis-regulation (A). Significant TFs from each model indicated TFs driving differential expression and chromatin states between conditions through direct epigenetic or transcriptome regulation.