Fig. 6: Transcriptional states complement chromatin accessibility to help prioritize causal cell types and genes mediating AD GWAS risk variants.
From: Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers
a Overview of prioritized risk genes by AD GWAS studies and their transcriptional changes across cellular states (absolute log2 fold-change in any cellular state for cell type). The “Locus” row indicates genes within the same locus using alternating black and gray rectangles. The color of the squares represents the max log2 fold-change of the gene between cell states (subclusters) of that cell type (gray: not significant). The square size represents the average log10 transformed gene expression. Borders represent co-accessibility (red background) or overlap (black outline) between the TSS and a regulatory element containing a prioritized (95% credible set) AD variant. Background color intensity corresponds to the highest posterior probability of association (PPA) of the 95% credible set variants overlapping the TSS or co-accessible element. b Replication of the parietal lobe differential expression results using the UCI prefrontal cortex snRNA-seq data. OR: Fisher exact test odds-ratio (replicated vs. non-replicated). c Distribution of genes co-accessible or with their TSS overlapping a regulatory element (snATAC-seq narrow peak) containing a fine-mapped AD risk genetic variant. The color indicates the number of cell types the co-accessibility signal was detected in. d Chromatin accessibility signals across cell types for the BIN1 locus. The lead variant is represented by a red vertical bar, and the fine-mapping PPAs are plotted for each variant with PPA >0.01. TSS regions co-accessible with variant-overlapping regulatory elements are plotted as arcs below each signal track. e Same visualization as (d) for the NCK2 locus. Source data are provided as a Source Data file.
