Fig. 4

Link between pleiotropic gene candidates and hematopoiesis. a Graph showing the proportion of pleiotropic variants (all cancers included) mapped in enhancers from immune cell types and blood (X-axis). The pink dots indicate significant overlap, as indicated in the inset. The variant-enhancer overlap proportions in brain and adipose tissue are indicated by red and blue horizontal dashed lines, respectively. b Graph showing the overrepresented (−log₁₀ FDR-adjusted p) genomic regulatory features (binding of transcription factors and defined histone marks, denoted in the inset) in the genomic sequences centered (± 10 base pairs) on the identified pleiotropic variants (n = 4,093). c Forest plot showing the OR and 95% CI of the overlap between the pleiotropic gene set and hematopoiesis gene modules, depicted by the corresponding master regulators (Y-axis). Red bars indicate significant overlap. d Uniform Manifold Approximation and Projection (UMAP) of the pleiotropic gene signature expression (score indicated in inset) in the bone marrow single-cell RNA sequencing profiles. Cell clusters are annotated. e Violin plot showing the distribution of the pleiotropic signature expression score in each bone marrow cell type (X-axis). The horizontal line corresponds to the average score of 100 random equivalent gene sets. The asterisks indicate a significant expression difference in the pleiotropic gene signature relative to equivalent random gene sets (**p_empirical < 0.01). f Venn diagram showing the overlap between mouse gene orthologs that, when mutated, cause immune system alterations (MP:0005387; “immune system phenotype”) and the pleiotropic gene set (all cancers included). The OR and significance (p_{hypergeometric}) are indicated. g Venn diagrams showing the overlap between mouse gene orthologs linked to myeloid cell alterations (phenotypes are indicated) and the pleiotropic gene set (all cancers included). The OR and significance (p_{hypergeometric}) value are indicated; n.s., not significant