Fig. 2: Sparse decomposition of arrays (SDA) component characterization.

a Notched box plots show SDA component C80 and C109 scores for post-mortem data samples in SCZ and NC groups (n  =  229 individuals; 145 NC and 84 SCZ). These were the only components showing a significant group effect. Group medians (horizontal line), 95% confidence intervals (notches), interquartile range (box edges), and whiskers (25^th/75^th percentiles or extrema) are shown. The scatter plot demonstrates SDA component C80 and C109 scores as a function of polygenic risk for schizophrenia and includes a regression fit line with mean fitted values and related shaded 95% confidence interval shown (n = 103 individuals; 64 NC and 39 SCZ). C80 is the only one with a significant PRS association consistent with diagnosis direction. Source data are provided as a Source Data file. b Gene enrichment analysis results are shown for the C80 component. From the bottom, the first (GWAS), second (MAGMA), and third orange grids (H-MAGMA) show enrichment results for schizophrenia risk genes, other psychiatric illness risk genes, and immune condition risk genes. Enrichment testing results are shown for differentially expressed genes, differentially methylated genes, and loss of function variant intolerant genes in the green grid. The final light-blue grid shows C80 tissue specificity as determined by the tissue scores generated during the SDA process and reflects the relative contribution of component gene networks within each of the sampled regions to the overall component. Adjusted p-values shown are empirical p-values obtained from permutation tests (overrepresentation analysis: one-sided Fisher exact test). c Venn diagram shows the intersection between C80 genes and SCZ, MDD, and ADHD GWAS risk genes. Blank regions indicate no common genes. In the case of a single gene result, that gene is listed. d Cell-type specificity of C80 component using human (left) and mouse (right) single-cell atlases. Mean-rank Gene Set Test in the limma R package¹¹⁵ was used to obtain the enrichment p-values shown. y-axes show FDR-adjusted p-values after correcting for multiple comparisons across components (N = 69) and cell types (human atlas = 10; mouse atlas = 24). Red dashed lines represent α_[FDR] = 0.05. Individual data points are shown using overlaid dot plots. Barplots demonstrate a higher specificity for GABAergic, medium spiny, and dopaminergic neurons. Source data are provided as a Source Data file. ADHD attention deficit hyperactivity disorder, ASC astrocytes, ASD autism spectrum disorder, BD bipolar disorder, CD Crohn’s disease, CN Caudate Nucleus, DEGs differentially expressed genes, DLPFC dorsolateral prefrontal cortex, DMGs differentially methylated genes, END endothelial cells, HP hippocampus, exCA pyramidal neurons from the hippocampal CA region, exDG granule neurons from the hippocampal dentate gyrus, exPFC pyramidal neurons from the prefrontal cortex, GABA GABAergic interneurons, LoF loss of function intolerant genes, MDD major depressive disorder, MG microglia, NC Neurotypical controls, NSC neuronal stem cells, OCD obsessive-compulsive disorder, ODC oligodendrocytes, OPC oligodendrocyte precursor cells, PRS polygenic risk score as reported by the third wave (primary) analyses of the Psychiatric Genetics Consortium²; PTSD posttraumatic stress disorder, SA suicide attempt, SCZ Patients with schizophrenia, UC ulcerative colitis.