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. 2024 Nov 21;56(12):2646–2658. doi: 10.1038/s41588-024-01952-y

Fig. 5. Integration of genomics and transcriptomics identifies genes and biological mechanisms in DCM.

Fig. 5

a,b, Partitioned heritability at tissue level (a) and at cell type level (b) from snRNA-seq data of 52 DCM cases and 18 controls. Enrichment P values were adjusted using the Benjamini–Hochberg method. Dashed line indicates FDR-adjusted P value of 0.05. For cell-type-specific heritability enrichment, cardiomyocyte marker and disease-specific expression in cardiomyocytes and mural cell types remained significant when the tau coefficient was used (Supplementary Table 16). c, Cell type expression of prioritized genes in single-nucleus transcriptomics from LV tissue in 18 control donors. Mean expression is scaled from minimum to maximum, and the proportion of expressing nuclei within a cell type is indicated by dot size. Cardiomyocyte expression is indicated in the gray shaded box. d, Differential expression of candidate genes across the range of major cell types. Red and blue indicate increased and reduced gene expression in DCM compared with controls, respectively. Yellow dot indicates significant DEGs within a cell type at FDR < 0.05. Genes are ordered by highest absolute log fold-change difference across cell types. Cell types are ordered by abundance from greatest (outer) to least (inner). e, Increased COL4A1 signaling from fibroblasts to cardiomyocytes, fibroblasts and mural cells via integrins from DCM single-nucleus transcriptomics. Communication probability indicates the scaled strength of interaction from maximum to minimum signaling interactions between cell types. Dot color reflects communication probabilities, and dot size represents P values computed by one-sided permutation test. f, Upregulation of BMP6 (ligand) in endocardial cells, resulting in increased signaling through BMPR1A in cardiomyocytes, fibroblasts and mural cells. Communication probability indicates the scaled strength of interaction from maximum to minimum signaling interactions between cell types. Dot color reflects communication probabilities, and dot size represents P values computed by one-sided permutation test. NC, neuronal cell; AD, adipocyte; FC, fold change; CNS, central nervous system; Max., maximum; Min., minimum.