Fig. 4: Genetics, transcriptomics and neuroimaging of autism and schizophrenia were consistently and specifically linked to normative transcriptional programs.

a, First row: cortical volume shrinkage in ASD, MDD and schizophrenia (SCZ) cases. Red indicates greater shrinkage, computed as z-scores of centiles from normative modeling of more than 125,000 MRI scans. Second row: AHBA components projected into the same Desikan–Killiany parcellation. b, Spatial correlations between volume changes and AHBA components, C1–C3. Significance was tested by two-sided FDR-adjusted spatially autocorrelated spin permutations and corrected for multiple comparisons. c, Enrichments in C1–C3 for consensus lists of DEGs in postmortem brain tissue of donors with ASD, MDD and SCZ compared to healthy controls (Methods). Significance was assessed as percentile of mean weight of DEGs in each component relative to randomly permuted gene weights and corrected for multiple comparisons; two-sided FDR-adjusted P values. d, Enrichment in C1–C3 for GWAS risk genes for ASD⁶⁶, MDD⁶⁷ and SCZ⁶⁸, tested for significance as in c, demonstrating alignment with both spatial associations to volume changes and enrichments for DEGs. e, Venn diagrams showing the lack of overlap of DEGs and GWAS risk genes reported by the primary studies summarized in c and d. f, DEGs and GWAS risk genes for each disorder were filtered for only C3-positive genes and then tested for enrichment with marker genes for each cortical layer³⁷. Significance was tested by one-sided Fisher’s exact test and corrected for multiple comparisons across all 42 tests. C3-positive DEGs and GWAS genes for SCZ (but not ASD or MDD) were both enriched for L2 and L3 marker genes, despite the DEGs and GWAS gene sets having nearly no overlap for each disorder (see Extended Data Fig. 6 for more detail). g, Convergent with L2/L3 enrichment in the C3-positive SCZ-associated DEGs and GWAS genes, a cortical map of supragranular-specific cortical thinning in SCZ⁷² was significantly and specifically co-located with C3 (r = 0.55, two-sided spin-permutation P = 0.002); each point is a region, and color represents C3 score. *P < 0.05, **P < 0.01, ***P < 0.001.