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. We performed a high-throughput snRNA-seq experiment on human postmortem 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 of the same cells, we also performed an sn-multiome analysis from these same caudate samples. Sn-multiome experiments have been used in recent years to study human brain development34,35 and neuropsychiatric diseases such as Alzheimer’s disease,36,37 but these studies have been limited by small sample sizes or shallow sequencing approaches, or studies in which sn-multiome data were supplemented with single-cell data generated in separate datasets.38 Here, we performed both a sn-multiome and a deep high-throughput snRNA-seq experiment in the same large sample cohort, allowing us to both robustly identify rare cell types and measure small differences in both gene expression and chromatin accessibility in the same nuclei.
