interaction between sex and OUD across genes and cell types to identify cell type-specific gene expression changes occurring in only males or females of individuals with OUD. Consistent with our analysis on the main effect of sex in OUD, we found more DEGs in glia (291 ± 55) than neurons (97 ± 5.6) with sex-specific changes in OUD (FDR < 0.05, Supplementary Data 1–S12). Among glial cell types, more DEGs were identified in females with OUD relative to males (Fig. S13). The complete set of gene alterations associated with OUD and sex are reported in Supplementary Data 1–S12. Lastly, we identified DEGs that were different between females and males within unaffected individuals and individuals with OUD. As expected, sex-specific DEGs in individuals with OUD compared to unaffected individuals were largely different, suggesting gene alterations dependent on sex and diagnosis were independent of naturally occurring gene expression variations between sexes (Fig. S14). Collectively, our findings indicated that many genes altered in OUD depend on sex across striatal cell types, especially across subtypes of glial cells.
