Fig. 4.

Cell-type-specific alterations of PD-associated genes and pathways. a Differential expression of PD-associated genes (associated by mutations reported to cause PD) across cell types and pairwise comparisons of disease groups with the control group. Fill of the tile indicates the log₂(fold change), with non-significant results (FDR > 0.05) coloured grey. b UMAP plot of excitatory and inhibitory neurons (upper panel, 102,293 nuclei), with SNCA expression levels (lower panel). c Ridgeline plot of distribution of SNCA expression levels in excitatory neurons across disease groups. Distributions have been split into 3 cumulative quantiles, highlighting, where 0–50%, 50–90% and 90–100% of the nuclei in each disease group lie. d Number of enriched pathways (FDR < 0.05) identified using cell-type-specific down- and up-regulated DE genes from each pairwise comparison together with 46 PD-associated pathways (associated in a large-scale polygenic risk score-based assessment of 2199 gene sets). DEG differentially expressed gene, GO gene ontology, OPC oligodendrocyte precursor cell, UMAP uniform manifold approximation and projection. PD-associated genes and pathways were derived from references [12, 16], respectively