Similar to our prior work2,4,5, we assembled a cohort of individuals diagnosed with OUD with a long history of opioid use (time since clinical diagnosis of at least four years), who also deceased from opioid overdose. Individuals with OUD were matched with unaffected individuals based on sex, age, postmortem interval (PMI), and RNA integrity number (RIN) (Supplementary Data 1-S5). Gene expression was aggregated across individual cell types to generate pseudobulk profiles for each major cell type. To identify differentially expressed genes (DEGs), gene expression profiles for each major cell type were compared between unaffected individuals and individuals with OUD, while covarying age, PMI, RIN, cell type abundance, gene detection rate, and surrogate variables. We identified 1,765 DEGs across cell types (197 ± 43 genes per cell type; FDR < 0.05; Fig. 2; Supplementary Data 1-S6), with more DEGs in glial cells relative to neurons (Fig. 2a, b).
