Fig. 3

Top differentially-expressed genes (DEGs) upregulated and down-regulated in LOAD by cluster and cell type. a, UMAP dimensional reduction plot of 33 cell subtype clusters based on snRNA-seq data. Clusters highlighted in panels b-d are circled in red. b–d, Unbiased volcano plots for six example clusters representing excitatory neuron (Exc), microglia (Micro), and oligodendrocyte (Oligo) cell types. Log₂ fold change (FC) between LOAD and normal control (NC) samples is plotted against –log₁₀ p-value (FDR). Points representing DEGs with statistically significant (p < 0.05) upregulation in LOAD are shown in green while DEGs with significant downregulation are shown in red. Genes without significantly differential expression are shown in blue. The proportion of DEGs to total genes examined is shown above each plot. The six DEGs with the highest absolute fold change (log₂FC > 0.2) in the up- and downregulated categories are labeled in green and red, respectively. The top up- and downregulated DEGs within 500 kb of disease-associated SNPs previously identified in GWAS are labeled in teal and pink, respectively. For each of the labeled genes, dot plots are shown below representing their unscaled expression levels (color) and percent of cells expressing the gene (width) for LOAD and NC samples. e, Heatmap showing log₂ FC for the top three DEGs with the highest log₂ FC values > 0.2 in at least one cell type in upregulated (green) and down-regulated (blue) categories for each cell type examined, as well as the top three DEGs (log₂FC > 0.2 in at least one cell type) within 500 kb of identified GWAS SNPs (labeled in purple). f, The top ten enriched GO terms for downregulated LOAD genes (FDR adjusted p < 0.5) for oligodendrocytes and downregulated LOAD genes for microglia. Statistical significance threshold of category enrichment (FDR < 0.05) indicated by vertical lines. g, Table and Venn diagrams comparing cell type level DEGs identified in this study to those of Morabito et al. [43] and Anderson et al. [44] Consensus DEGs were identified in 2 or more studies