Table 2.
Gene Network Analyses of 139 Findings From MWAS of Schizophrenia
| Variable | Significant Genes in MWAS | Totala | Genes,b No. | Enrichmentc | P Value |
|---|---|---|---|---|---|
| Protein-protein interaction | |||||
| IgA1 | FCAR, RUNX3, CREB1, SMAD3 | 19 | 4 | 23.8 | 4.6 × 10−6 |
| elf5 | FRZB, SS18L1, RPS15A | 10 | 3 | 34.0 | 2.5 × 10−5 |
| EPAS1 | ARNT, SMAD3 | 2 | 2 | 113.2 | 3.7 × 10−5 |
| RhoG |
CHN2, TIAM1, ARHGAP15, PIK3R3, ARHGAP26, RHOH GDI2 |
153 | 7 | 5.2 | 4.1 × 10−5 |
| ETS1 | RUNX2, ETS2, SMAD3, CREB1, ARNT | 76 | 5 | 7.4 | 9.8 × 10−5 |
| Chp | TIAM1, CHN2, ARHGAP15, ARHGAP26, RHOH, GDI2 | 127 | 6 | 5.3 | 1.2 × 10−4 |
| mtf2 | PRKD2, CREB1, SMAD3 | 17 | 3 | 20.0 | 1.4 × 10−4 |
| PEBPB2 | RUNX2, RUNX3, SMAD3 | 20 | 3 | 17.0 | 2.3 × 10−4 |
| PKC-delta |
PPM1D, INPP5D, TIAM1, PPARA, RUNX2, CHN2, CXCR4 PHLPP1 |
274 | 8 | 3.3 | 2.6 × 10−4 |
| EP300 |
RUNX2, TRERF1, ARNT, PPARA, CREB1, SMAD3, ETS2 RUNX3, SS18L1, SATB1, TCF12, BRD4 |
616 | 12 | 2.2 | 3.5 × 10−4 |
| Pathway | |||||
| Signaling by Rho GTPases | TIAM1, CHN2, ARHGAP15, ARHGAP26, RHOH, GDI2 | 126 | 6 | 3.3 | 1.1 × 10−4 |
| PIP3 activates AKT signaling | MAPKAP1, PHLPP1, CREB1 | 28 | 3 | 7.5 | 6.2 × 10−4 |
| HIF1A transcription factor network |
SMAD3, CXCR4, CREB1, ARNT | 66 | 4 | 4.3 | 6.6 × 10−4 |
| Regulated nuclear SMAD2/3 signaling |
RUNX2, RUNX3, CREB1, SMAD3 | 78 | 4 | 3.6 | 1.2 × 10−3 |
| Signaling by SCF-KIT | MAPKAP1, PHLPP1, PIK3R3, CREB1 | 78 | 4 | 3.6 | 1.2 × 10−3 |
| Pyrimidine salvage reactions | UPP2, UCK2 | 9 | 2 | 15.6 | 1.3 × 10−3 |
| Androgen receptor | RUNX2, SMAD3, KDM3A, CREB1, ARNT | 146 | 5 | 2.4 | 1.9 × 10−3 |
| Wnt core | FRZB, CREB1, SMAD3 | 44 | 3 | 4.8 | 2.3 × 10−3 |
| Fcγ-mediated phagocytosis | FCGR2B, PIK3R3, INPP5D, FCGR2C | 95 | 4 | 3.0 | 2.6 × 10−3 |
| Erythropoietin neuroprotective NF-κB |
CREB1, ARNT | 13 | 2 | 10.8 | 2.7 × 10−3 |
| microRNA | |||||
| miR-376c | ARNT, FAM63B, BRD4, MYT1L, TIAM1, SATB1, ACSL1 | 155 | 7 | 5.2 | 4.0 × 10−4 |
| miR-217 |
GDI2, TCF12, PPM1D, AFF3, SATB1, RUNX2, BRP44L CHN2 |
234 | 8 | 3.9 | 9.9 × 10−4 |
| miR-19 |
RUNX3, PIK3R3, MBD6, NDFIP2, DAAM1, MYT1L, TIAM1 PPARA, SATB1, RBMS3, FOXP1, FNDC3B, NAALADL2 ACSL1, NUS1, CSPP1 |
923 | 16 | 2.0 | 7.7 × 10−3 |
| miR-218 |
CSDE1, ARL3, MBD6, CHFR, DAAM1, FOXN3, RCOR1 TCF12, FAM63B, MYT1L, RASSF2, ACSL1, RUNX2 |
689 | 13 | 2.2 | 8.4 × 10−3 |
| miR-9 |
PIK3R3, BTBD10, TRAPPC6B, FOXN3, RCOR1, FAM63B PPARA, TBC1D22A, RBMS3, FOXP1, FNDC3B, IPO11 NUS1, MTHFD1L, AUH |
926 | 15 | 1.8 | 2.3 × 10−2 |
| miR-544 | PIK3R3, CSDE1, PELI2, RCOR1, SATB1, FOXP1, MLL3 | 339 | 7 | 2.4 | 2.9 × 10−2 |
| miR-504 | ARNT, FAM63B, MYT1L, FOXP1 | 138 | 4 | 3.3 | 3.3 × 10−2 |
| miR-181 |
PIK3R3, ARL3, RCOR1, TMEM131, CREB1, RASSF2 SS18L1, PPARA, FOXP1, NAALADL2, GNB4, ACSL1, NUS1 MLL3 |
883 | 14 | 1.8 | 3.4 × 10−2 |
| miR-135 |
PIK3R3, ARNT, MBD6, PELI2, FOXN3, RCOR1, MYT1L NAALADL2, MAN1A1 |
505 | 9 | 2.0 | 4.2 × 10−2 |
| miR-203 |
MBD6, TRAPPC6B, SMAD3, SS18L1, ETS2, FOXP1 NSUN7, ACSL1, RUNX2 |
548 | 9 | 1.9 | 5.7 × 10−2 |
Abbreviation: MWAS, methylome-wide association study.
a
Total number of genes in the network.
b
Number of genes in the network with q < 0.01 in the MWAS.
c
Calculated as the proportion of genes observed in the network vs the proportion of genes expected assuming no enrichment.