In this study, we present a large-scale 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 snRNA-seq with chromatin accessibility profiling (ATAC-seq) within the same cells at large scale, using both sn-multiome and snRNA-seq experiments, we discovered unique patterns of gene expression within different cell types and distinct regulatory mechanisms underlying them. This integrative approach demonstrates the power of large-scale multiomic studies to uncover cell-type-specific regulatory mechanisms in complex brain disorders, and can be applied to investigate other neuropsychiatric and neurodegenerative conditions.
