The caudate harbors multiple cell types31, and cell-type-specific characterization of the AUD-associated transcriptome in the human caudate is lacking. To meet this gap in knowledge, we sought to provide a comprehensive view of AUD-related differences in gene expression and chromatin accessibility in specific cell types within the human caudate nucleus and infer mechanisms underlying these changes. Single-nucleus multiome experiments (sn-multiome), assaying both chromatin accessibility and gene expression within the same cell, provide remarkable opportunities to draw causal inferences regarding mechanisms underlying AUD-associated gene expression. We performed a high-throughput snRNA-seq experiment on human post-mortem samples from the caudate nucleus of 143 donors, 74 with and 69 without AUD, obtaining transcriptomic data from over 1.1 million cells. To compare the transcriptome with the open chromatin status within the same cells, we also performed an sn-multiome (snRNA-seq + assay for transposase-accessible chromatin with sequencing (ATAC-seq32)) analysis from these same caudate samples, allowing us to both identify uncommon cell types and unique cell states, and measure small differences in both gene expression and chromatin accessibility in the same nuclei. We profiled the biological pathways
