To test the functional impact of our SCZ-associated predicted gene expression changes (GREX), we performed two in-silico analyses. First, we compared differentially expressed genes in the Fromer et al. CMC analysis to DLPFC prediXcan results; 76/460 are nominally significant in the DLPFC prediXcan analysis, significantly more than would be expected by chance (binomial test, p = 8.75 × 10−20). In particular, the Fromer et al. analysis highlighted six loci where expression levels of a single gene putatively affected schizophrenia risk. All six of these genes are nominally significant in our DLPFC analysis, and two (CLCN3 and FURIN) reach genome-wide significance. In the conditional analysis across all brain regions, one additional gene (SNX19) reaches genome-wide significance. The direction of effect for all six genes matches the direction of gene expression changes observed in the original CMC paper, indicating that gene expression estimated in the imputed transcriptome reflects measured expression levels in brains of individuals with schizophrenia. Further, this observation is consistent with a model where the differential expression signature observed in CMC is caused by genetics rather than environment.
