showing the prioritization and functional categories for all possible modules associated with various traits (fig. S50).] In particular, we found that cross-disorder prioritized modules are associated with functional categories such as “immune processes,” “synaptic activity,” and “splicing,” consistent with the findings from more disease-focused analyses (Fig. 8C) (22). Also, we showed that prioritized SCZ and BPD modules are enriched for known GWAS SNPs (fig. S51) (for ASD, the lack of GWAS SNPs precludes similar analyses). For SCZ, which is the best characterized of the three disorders, we find enrichments for pathways and genes known to be associated with the disease, including glutamatergic-synapse pathway genes, such as GRIN1; calcium-signaling pathway and astrocyte-marker genes; and complement cascade pathway genes such as C4A, C4B, and CLU (Fig. 8D) (22). Other prioritized modules include well-characterized genes such as MIAT, RBFOX1, and ANK2 (SCZ); RELA, NFkB2, and NIPBL (ASD); and HOMER1 (BPD), consistent with the results of (22). Finally, we identify modules associated with aging, finding that they are enriched in Ex4 neuronal cell-type genes, synaptic and longevity functions, and the gene NRGN—all consistent with differential expression analysis (Fig. 8D and fig. S20).
