Table 4.
Top-ranking significant gene sets from the discovery analysis
| Source | Gene set | Type | CNVs >100Kb | CNVs >500Kb | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Name | Genes | # CNVs | OR | 95% CI | Pemp | Genes within CNVs (genes) | CNVs | OR | 95% CI | Pemp | Genes within CNVs (genes) | ||
| KEGG | hsa04660 T cell receptor signaling pathway | 108 | DEL | 29 | 4.42 | (1.61, 12.2) | 1e-04 | CBLB,DLG1,LAT,MAP3K14,MAP3K7,MAPK3,NFAT5,NRAS,PAK2,PDCD1,PPP3CA,RELA,VAV3 (13) | 19 | 15.72 | (0.87, 285) | 4e-05 | CBLB,DLG1,LAT,MAP3K7,NFAT5,PAK2,PPP3CA (7) |
| KEGG | hsa04640 Hematopoietic cell lineage | 85 | DEL | - | - | - | 17 | 14.4 | (1.9, 109) | 2e-05 | CD19,CD36,GP1BB,IL7R,TFRC (5) | ||
| KEGG | hsa04621 NOD-like receptor signaling pathway | 58 | DUP | 22 | 9.27 | (2.17, 39.7) | 1e-05 | CCL5,CXCL1,CXCL2,ERBB2IP,HSP90AA1,IL8,MAPK3,MAPK8,NAIP,NLRC4,RIPK2 (11) | 15 | 7.05 | (1.6, 31) | 2e-04 | CXCL1,CXCL2,IL8,MAPK3,MAPK8,NAIP,RIPK2 (7) |
| TargetScan | hsa-miR-10a | 144 | DEL& DUP | - | - | - | - | - | 50 | 2.86 | (1.54, 5.32) | 3e-05 | AP002478.1,BCL2L11,BCR,C10orf68,C16orf54,CEP350,CLEC18A, CNST,COL4A4,CSMD1,ELOVL2, EPHA2,GJA5,LCA5,PVRL3,SDPR,SLCO4C1,TFRC,TIAM1,ZNF254 (20) |
| GO | GO:16458 gene silencing | 71 | DEL | 14 | 31.52 | (1.67, 595) | 1e-05 | DGCR8,ERI1,NCBP2 (3) | 14 | 28.21 | (1.48, 537) | 1e-05 | DGCR8,ERI1,NCBP2 (3) |
| GO | GO:2000602 regulation of interphase of mitotic cell cycle | 162 | DEL | 17 | 17.34 | (2.31, 130) | 1e-05 | ATM,CDC45,DLG1,PRMT2,RPL24,USP17L2 (6) | 13 | 26.17 | (1.36, 504) | 1e-05 | CDC45,DLG1,RPL24 (3) |
| GO | GO:42471 ear morphogenesis | 99 | DEL | 12 | 28.67 | (1.5, 548) | 5e-05 | CDH23,GBX2,PTPRQ,SOBP,TBX1 (5) | - | - | - | - | - |
| GO | GO:14069 postsynaptic density | 100 | DEL | - | - | - | 25 | 6.74 | (1.66, 27.3) | 1e-05 | DLG1,DLGAP1,FBXO45,LIN7A,MAGI2,P2RX6,SEMA4C (7) | ||
| GO | GO:16327 apicolateral | 109 | DEL | - | - | - | 24 | 9.61 | (2.23, 41.4) | 1e-05 | CLDN23,CLDN5,DLG1,FRMPD2, JAM2,LIN7A,MAGI2,MICALL2,PMP22,PVRL3 (10) | ||
| GO | GO:287 magnesium ion binding | 179 | DEL | - | - | - | 24 | 6.71 | (1.66, 27.1) | 2e-05 | ABL2,COMT,FAN1,MAP3K7,NT5C3,STK38L,TSSK2 (7) | ||
| GO | GO:32526 response to retinoic acid | 101 | DEL | - | - | - | 14 | 28.67 | (1.51, 546) | 1e-05 | ABL2,PDGFA,TBX1,TFRC (4) | ||
| GO | GO:10498 proteasomal protein catabolic process | 190 | DUP | - | - | - | 23 | 8.39 | (2.51, 28.1) | 2e-05 | ANAPC1,CRBN,DERL3,FBXO45, KCTD13,MAD2L1,PSMA7,STUB1,UBB,WWP2 (10) | ||
| GO | GO:16052 carbohydrate catabolic process | 131 | DUP | - | - | - | 14 | 6.88 | (2.04, 23.3) | 2e-05 | AGL,ALDOA,ALDOB,HK2,OGDHL,PGM1 (6) | ||
| GO | GO:16585 chromatin remodeling complex | 114 | DUP | - | - | - | 22 | 26.31 | (3.58, 194) | 1e-05 | BAZ1B,DPY30,HDAC9,INO80B,INO80E,NCOR1,SMARCA2,SMARCB1,USP22 (9) | ||
| GO | GO:2755 MyD88-dependent toll-like receptor signaling pathway | 75 | DUP | - | - | - | 14 | 17.55 | (2.35, 131) | 1e-05 | MAP2K3,MAPK3,MAPK8,RIPK2, UBB (5) | ||
The number of genesets (N) tested within each database: KEGG: N=228, TargetScan: N=87, and GO: N=1499. All the gene sets listed here were significantly enriched in cases than in controls based on p-values. For KEGG and TargetScan, all have q-value <0.01 implying that <1% of significant tests or <0.27 test will result in false discoveries; and for GO, all have q-value <0.004, implying that <0.4% of significant tests or <0.59 test will result in false discoveries. DEL: deletions. DUP: duplications. All tests were one-sided assuming enrichment in cases using genic CNVs. #CNV = the number of events that overlapped any gene in the geneset by ≥1bp. #genes = the number of unique genes in the geneset that had at least 1 genic CNV hit (≥1bp overlap). OR=odds ratio, indicating the increase in risk for schizophrenia correcting for rate and size of genic CNVs and genotyping batch effect (a continuity correction applied if necessary). CI: confidence interval. Pemp, empirical P values were obtained in PLINK by 100,000 permutations and permuting phenotype labels within genotyping batches.