Fig. 6: Sex-biased transcriptional alterations in striatal cell types associated with OUD.

a Barplot showing the number of differentially expressed genes (DEGs) detected by cell type in sex-specific differential analyses comparing unaffected individuals and individuals with OUD. The bar plots show significant DEGs in only female individuals, in only male individuals, or in both groups (FDR < 0.05). b Network plot of significant clusters and enriched pathways as in Figs. 2b, c and 4b, c. Here, enriched pathways include only DEGs calculated within female individuals if less significant than those calculated within male individuals. Pathways with a square point are also enriched using an alternate calculation of a sex-interaction score. c Boxplots showing sex- and cell type-specificity of differential expression of FKBP5. The boxplot labels the log2(counts per million) normalized gene expression values regressing out covariates and surrogate variables. Each point is a biological replicate colored by diagnosis (*P_{Dx within Sex} < 0.05; **P_{Dx within Sex} < 0.01; ***P_{Dx within Sex} < 0.001, two-sided limma regression, exact P-values reported in Supplementary Data 1–S12). Each data point consists of N = 22 caudate and putamen samples from M = 12 individuals. d A sunburst plot representing curated synaptic gene sets from SynGO from genes enriched in cluster 6, a female-biased set of pathways enriched in astrocytes. e A network plot as in (b); however, displaying the male-biased pathways. f Diagram showing the male biased DEGs that are components of the electron transport chain, including genes involved in mitochondrial functions (NDUFA4, NDUFB7, and NDUFA13 of complex I of mitochondrial respiratory chain; UQCR11 and UQCRQ of complex II; and COX6B1 of complex IV). Schematics in (f) created using BioRender.com. Source data are provided as a Source Data file. Boxplots in 6 C are plotted as median, the 25% and 75% percentiles, and non-outlier maxima and minima.