Figure 6.
Combinatorial effects of variants on global transcriptome in schizophrenia
(A) Risk alleles of four MPRA-positive variants in the SETD8 locus downregulate the reporter gene compared with protective alleles.
(B) SETD8 expression levels in excitatory neurons of postmortem schizophrenia brains. p values were obtained from Ruzicka et al.42
(C) The extent of dysregulation of SETD8 co-expressed genes in excitatory neurons of postmortem schizophrenia brains. Significant upregulation and downregulation (padjusted < 0.05) are highlighted in red and blue, respectively. Z scores were calculated from permutation.
(D) Genes upregulated by SETD8 knockdown were enriched for genes upregulated in excitatory neurons (Ex-L3 and Ex-L6b_SEMA3E) of postmortem schizophrenia brains. Significant enrichment (FDR < 0.05) for upregulated and downregulated genes in response to SETD8 perturbation is highlighted in red and blue, respectively. p values were calculated by two-sided Fisher’s exact test.
(E) Risk alleles of three MPRA-positive variants in the MEF2C locus upregulate the reporter gene compared with protective alleles.
(F) MEF2C expression levels in excitatory neurons of postmortem schizophrenia brains. p values were obtained from Ruzicka et al.42
(G) The extent of dysregulation of MEF2C co-expressed genes in excitatory neurons of postmortem schizophrenia brains. Significant upregulation and downregulation (padjusted < 0.05) are highlighted in red and blue, respectively. Z scores were calculated from permutation.
(H) Genes downregulated by Mef2c knockout were enriched for genes upregulated in excitatory neurons of postmortem schizophrenia brains. Significant enrichment (FDR < 0.05) for upregulated and downregulated genes in response to Mef2c perturbation is highlighted in red and blue, respectively. p values were calculated by two-sided Fisher’s exact test.