In addition to inherited differences, the extended, excessive use of alcohol characteristic of AUD is likely to alter gene expression and chromatin conformation. While microarray and bulk RNA sequencing (RNA-seq) studies have identified differentially expressed genes (DEGs) in human cell lines9–12 and in several brain regions in rat13–20 and human post-mortem tissue10,21–23, bulk studies obscure the unique transcriptional signatures of individual cell types within the brain. Single-cell/single-nucleus RNA sequencing (snRNA-seq) has enabled measurement of the distribution and characterization of different cell types in a tissue sample and of gene expression within each of these individual cells. An early snRNA-seq study of nuclei from the prefrontal cortex of seven individuals identified seven major cortical cell types and found differences in expression associated with AUD within six cell types24.
