DLPFC and Hippocampus Differential Gene Expression in Schizophrenia

1. SUPPLEMENTARY FIGURE 1. COVARIATES IN DLPFC DIFFERENTIAL EXPRESSION ANALYSIS Figure S1A R=-.92, p<2.2x10-16 R=-.86, p<2.2x10-16 R=-.01, p=0.86 RIN Effect On Expression Diagnosis Effect on Expression (No covariates) Diagnosis Effect on Expression (Covariates: AGE+SEX+RIN) Diagnosis Effect on Expression (Covariates: 9PCs) Figure S1B SEX AND DIAGNOSIS AGE AND DIAGNOSIS CONT (n=86) SCZ (n=80) t-stat=-0.69, p-value = 0.49

2. SUPPLEMENTARY FIGURE 2. DLPFC DIFFERENTIAL EXPRESSION, BY IMMUNE GENE SET (A) DIFFERENTIAL EXPRESSION, BY IMUNE GENE SET (CAUC) Before multiple testing correction After Bonferonni correction p=0.05 Wilcoxon Test -log10(p-value) (B) DIFFERENTIAL EXPRESSION, BY IMUNE GENE SET (AA+CAUC) Before multiple testing correction After Bonferonni correction (a) DIFFERENTIAL EXPRESSION, BY IMUNE GENE SET (AA+CAUC) p=0.05 Wilcoxon Test -log10(p-value) IFN IFN IFN IFN TNF TNF TNF TNF BBB BBB BBB BBB TGFB TGFB TGFB TGFB NFKB NFKB NFKB NFKB T REG T REG T REG T REG NK CELL NK CELL NK CELL NK CELL MICROGLIA MICROGLIA MICROGLIA MICROGLIA CYTOTOXIC T CYTOTOXIC T CYTOTOXIC T CYTOTOXIC T CHEMOKINES CHEMOKINES CHEMOKINES CHEMOKINES EICOSANOIDS EICOSANOIDS EICOSANOIDS EICOSANOIDS INTERLEUKINS INTERLEUKINS INTERLEUKINS INTERLEUKINS COMPLEMENT COMPLEMENT COMPLEMENT COMPLEMENT B CELL RECEPTOR B CELL RECEPTOR B CELL RECEPTOR B CELL RECEPTOR OXIDATIVE STRESS OXIDATIVE STRESS OXIDATIVE STRESS OXIDATIVE STRESS OTHER CYTOKINES OTHER CYTOKINES OTHER CYTOKINES OTHER CYTOKINES T CELL RECEEPTOR T CELL RECEEPTOR T CELL RECEEPTOR T CELL RECEEPTOR INNATE IMM RECEPT INNATE IMM RECEPT NUCLEAR RECEPTORS NUCLEAR RECEPTORS NUCLEAR RECEPTORS NUCLEAR RECEPTORS INNATE IMM RECEPT INNATE IMM E RECEPT HEAT SHOCK PROTEINS HEAT SHOCK PROTEINS HEAT SHOCK PROTEINS HEAT SHOCK PROTEINS

3. SUPPLEMENTARY FIGURE 3. DLPFC DIFFERENTIAL EXPRESSION, BY RACE AA (n=110 CONT, n=65 SCZ) CAUC (n=86 CONT, n=79 SCZ) CCL28 ABCC4 PLA2G5 CXCL10 HSPA8 IL13RA2 GDF7 SNCA IL7 ESRRA NOS2 TNFRSF11A NLRP1 ESRRG CXCL5 GPR156 ACVR2A TNFRSF18 HSPA4 TSPAN2 SERPING1 TNFSF13 GHR AA+CAUC (n=196 CONT, n=144 SCZ)

4. SUPPLEMENTARY FIGURE 4. CORRELATION OF DLPFC GENE EXPRESSION WITH SCHIZOPHRENIA POLYGENIC RISK SCORE (A) CORRELATION OF INDIVIDUAL GENES WITH SCZ RPS TOP DIFFERENTIALLY EXPRESSED GENE IL13RA2 (B) CORRELATION OF PC1 OF DLPFC GENE GROUPS WITH SCHIZOPHRENIA RPS ALL IMMUNE (n=559 genes, PC1=25%) 1.5 Correlation of PC1 with SCZ RPS -log10pvalue 1.0 0.5 0 CYTOKINES (n=180 genes, PC1=33%) INNATE (n=142 genes ,PC1=37%) ADAPTIVE (n=69 genes, PC1=29%) OTHER (n=205 genes, PC1=26%) Correlation of PC1 with SCZ RPS -log10pvalue Note: S1-S10 p-value thresholds for polygenic risk score: s1=10E-8, s2=10E-6, s3=10E-4, s4=10E-3, s5=0.01, s6=0.05, s7=0.1, s8=0.2, s9=0.5, S10=1 Displayed p-values in table and plots are before multiple testing correction, Red Line is p=-log10(0.05) S1 S1 S1 S1 S1 S2 S2 S2 S2 S2 S3 S3 S3 S3 S3 S4 S4 S4 S4 S4 S5 S5 S5 S5 S5 S6 S6 S6 S6 S6 S7 S7 S7 S7 S7 S8 S8 S8 S8 S8 S9 S9 S9 S9 S9 S10 S10 S10 S10 S10

5. SUPPLEMENTARY FIGURE 5. NEURODEVELOPMENTAL TRAJECTORY OF IMMUNE GENES IN BRAINSPAN DATASET GENE EXPRESSION (% of Maxiumum for gene group) Age (Years)

6. SUPPLEMENTARY FIGURE 6. HIPPOCAMPUS DIFFERENTIAL EXPRESSION, BY IMMUNE GENE (A) DIFFERENTIAL EXPRESSION, BY GENE (CAUC) (B) DIFFERENTIAL EXPRESSION, BY GENE (AA+CAUC) FDR=0.05 FDR=0.05 –log10 p–value –log10 p–value FOLD CHANGE FOLD CHANGE N=517 Genes with RPKM>0.04 N=521 Genes with RPKM>0.04

7. SUPPLEMENTARY FIGURE 7. HIPPOCAMPUS DIFFERENTIAL EXPRESSION, BY IMMUNE GENE SET (A) DIFFERENTIAL EXPRESSION, BY IMUNE GENE SET (CAUC) Before multiple testing correction After Bonferonni correction p=0.05 Wilcoxon Test -log10(p-value) (B) DIFFERENTIAL EXPRESSION, BY IMUNE GENE SET (AA+CAUC) Before multiple testing correction After Bonferonni correction p=0.05 Wilcoxon Test -log10(p-value) IFN IFN IFN IFN TNF TNF TNF TNF BBB BBB BBB BBB TGFB TGFB TGFB TGFB NFKB NFKB NFKB NFKB T REG T REG T REG T REG NK CELL NK CELL NK CELL NK CELL MICROGLIA MICROGLIA MICROGLIA MICROGLIA CYTOTOXIC T CYTOTOXIC T CYTOTOXIC T CYTOTOXIC T CHEMOKINES CHEMOKINES CHEMOKINES CHEMOKINES EICOSANOIDS EICOSANOIDS EICOSANOIDS EICOSANOIDS INTERLEUKINS INTERLEUKINS INTERLEUKINS INTERLEUKINS COMPLEMENT COMPLEMENT COMPLEMENT COMPLEMENT B CELL RECEPTOR B CELL RECEPTOR B CELL RECEPTOR B CELL RECEPTOR OXIDATIVE STRESS OXIDATIVE STRESS OXIDATIVE STRESS OXIDATIVE STRESS OTHER CYTOKINES OTHER CYTOKINES OTHER CYTOKINES OTHER CYTOKINES T CELL RECEEPTOR T CELL RECEEPTOR T CELL RECEEPTOR T CELL RECEEPTOR INNATE IMM RECEPT INNATE IMM RECEPT INNATE IMM RECEPT INNATE IMM RECEPT NUCLEAR RECEPTORS NUCLEAR RECEPTORS NUCLEAR RECEPTORS NUCLEAR RECEPTORS HEAT SHOCK PROTEINS HEAT SHOCK PROTEINS HEAT SHOCK PROTEINS HEAT SHOCK PROTEINS

8. SUPPLEMENTARY FIGURE 8. POST-MORTEM DLPFC AND HIPPOCAMPUS DIFFERENTIAL EXPRESSION, MHC REGION (A) DLPFC MHC DIFFERENTIAL EXPRESSION (AA+CAUC) (B) HIPPOCAMPUS MHC DIFFERENTIAL EXPRESSION (AA+CAUC) FDR=0.05 -log10pvalue -log10pvalue FDR=0.05 Fold Change Fold Change n=170 Genes RPKM>0.04 n=146 Genes RPKM>0.04