In this study we present the first integrated profile at the single-nuclei level of differences between individuals with and without AUD in gene expression, chromatin accessibility, and cell state in the caudate nucleus, and determined potential regulatory mechanisms underlying these differences. By combining single-nucleus RNA sequencing (RNA-seq) with chromatin accessibility profiling (ATAC-seq) within the same cells at large scale, using both sn-multiome and snRNA-seq experiments, we discovered novel patterns of gene expression within different cell types and novel regulatory mechanisms behind them. This integrative dual approach demonstrates the power of large-scale multiomic studies to uncover cell-type-specific regulatory mechanisms in complex brain disorders. Such methodologies can be applied to investigate other neuropsychiatric and neurodegenerative conditions, expanding the utility of this approach across the field of neuroscience.
