Fig. 6

Assessing genes for regional divergence and disease association. a Region-specific divergent genes (blue) across all brain regions. Red bars represent genes with conserved co-expression in that region but divergent in another. The cerebral cortex displayed the greatest region-specific divergence whereas cerebellum displayed strongest region-specific conservation. b kME divergence of MID1 and ZER1 for each brain region. Each gene shows divergence in one region which significantly exceeds that from another region. Error bars represent the 95% CI from permuting across study in that species; * denotes divergent regions with a CI which does not overlap the CI of another region. c Proportion of each whole-brain consensus modules with region-specific divergent genes. Bar color indicates cell-type annotation of module. d The top 500 up- and downregulated genes for alcoholism (AAD), autism (ASD), bipolar disorder (BD), schizophrenia (SZ), and Alzheimer’s (AD) are plotted for their kME divergence and tested in enrichment for diverged genes (left). All disorders except for AAD show enrichment for diverged genes. Removing genes associated to an astrocytic (WB-M6) or microglial (WB-M8/WB-M10) module ablated the upregulated signature for ASD, SCZ, BD, and AD (right). e kME divergence of FOXO1 and RGS4 from the discovery GTEx dataset to both human and mouse datasets. FOXO1 and RGS4 are up- and downregulated respectively in SZ, BD, ASD, and AD and both display significantly increased kME divergence in mouse. Error bars represent the 95% CI from permuting across study in that species. f kME divergence of PSEN-1 and SNCA across all brain regions. Error bars represent the 95% CI from permuting across study in that species; * denotes regions with a CI that does not overlap zero. g Examples of genes diverged in at least one brain region and associated with major diseases and disorders investigated in this analysis