Extended Data Fig. 8: Single-nucleus gene expression/enrichment analysis and proteome-wide association study (PWAS) of stroke in brain tissue.
From: Stroke genetics informs drug discovery and risk prediction across ancestries
(A) Single-nucleus gene expression data of TWAS-COLOC genes in dorsolateral prefrontal cortex (ROS-MAP study)21; Dot plot of the mean expression level in expressing cells (colour) and percent of expressing cells (circle size) of selected genes across different cell types; (B) Proteome-wide association study (PWAS) of stroke in brain tissue; Box plot showing effect estimates (odds ratio) for associations of pQTL of ICA1L in the ROS-MAP (N = 376 independent samples) and Banner (N = 152 independent samples) studies with any stroke (AS) and any ischaemic stroke (AIS), identified in PWAS after multiple testing correction. Odds ratios ± 95% CIs are shown. Dashed line indicates an odds ratio of 1. Two-sided p-values were computed using the TWAS-COLOC approach. (C) Cell-type enrichment in human and mouse single cell RNA-seq databases using STEAP; the UpSet plot displays the number of significant enrichment results, by stroke subtype (horizontally; 2 for CES, 5 for AIS, 6 for AS, and 12 for LAS) and by cell subtype (vertically; 2 cell-types show significant enrichment in LAS, AIS, and AS, 2 cell-types in AIS and AS, and 1 cell-type in LAS and AS, while 9 cell-types show significant enrichment in LAS only, 2 in CES only and 1 in AS and AIS respectively); details are displayed in Supplementary Table 29. AS: any stroke; AIS: any ischaemic stroke; LAS: large artery stroke; CES: cardioembolic stroke; VLMC: vascular and leptomeningeal cells, OPC: oligodendrocyte progenitor cells, SMC: smooth muscle cells; VSMCA: vascular smooth muscle cells, arterial.
