Table 2.
Top KDs Based on CAD GWAS Enrichment in the KD Subnetworks
| KD | Subnetwork Size | No. of Genes With CAD 1000 Genomes GWAS P<0.001 in KD Subnetworks | Genes With CAD 1000 Genomes GWAS P<0.001 in KD Subnetworks | P Values Compared With GWAS Genes |
|---|---|---|---|---|
| SLIT3 | 28 | 11 | APOE, SLIT3, EPB41L2, NID1, FN1, TGFBR3, DOCK1, ADM, SCARA5, PROCR, THBS3 | <0.00114 |
| AZGP1 | 23 | 8 | PLG, SLC22A1, UPB1, APOA5, AZGP1, ABCG5, CYP2A13, FBP1 | <0.00114 |
| APOF | 45 | 17 | PLG, APOC4, ITIH3, GLS2, APOB, APOA5, ARG1, APOF, AGXT, LIPC, ITIH4, MAT1A, PAH, PON1, CFI, APOC2, CYP2A13 | <0.00114 |
| LDLR | 11 | 7 | APOE, APOB, LRPAP1, LDLR, PCSK9, DAB1, AP1M2 | <0.00114 |
| ACCN1 | 13 | 4 | LARGE, ACCN1, ITGA2, CYP17A1 | <0.00114 |
| RIF1 | 11 | 2 | MALAT1, NBEAL1 | <0.00114 |
| STAT3 | 102 | 35 | CDKN1A, PDGFRA, JUN, FGFR3, FLT1, CXCR4, RPS6KA5, BRCA1, HDAC3, STMN1, NLK, STAT5B, STAT3, ZNF467, MAP3K7, MTOR, NMI, RAC1, PML, KAT5, EIF2AK2, PRKCD, PTPN11, JAK3, FOXM1, PDGFRB, HNF1A, SUMO4, FES, IL2RA, IL6R, IGF1R, RELA, FER, ZNF148 | <0.00114 |
| OAS2 | 12 | 4 | IFIT1, APOA4, OAS1, MMP12 | <0.00114 |
| F2 | Adipose (49); muscle (47) | Adipose (12); muscle (19) | Adipose (PLG, SERPIND1, SEC14L2, APOC3, APOA5, APOA4, APOF, LIPC, PAH, AKR1C1, APOA1, F2); Muscle (PLG, SERPIND1, HPX, APOC3, ATP2A2, KLKB1, UPB1, TNNT1, APOA5, MYL2, ARG1, ASGR1, GNMT, MAT1A, PAH, AKR1C1, CFI, APOA1, F2) | Adipose (0.0182); muscle (0.00114) |
| HGD | Brain (40); muscle (48) | Brain (8); muscle (12) | Brain (PLG, APOC4, HPX, APOA5, APOF, PAH, AKR1D1, APOA1); Muscle (PLG, APOC4, CA5A, UROC1, APOC3, UPB1, APOB, APOA5, AGXT, MAT1A, CYP2A13, FBP1) | Brain (0.00114); muscle (0.0136) |
| LUM | 45 | 12 | CXCL12, COL3A1, TGFBR3, BMP6, FIBIN, TFPI, GBP1, ANXA4, SMOC2, SPOCK3, PCOLCE, ZFPM2 | 0.00114 |
| MTMR11 | 80 | 25 | DUSP8, ARHGAP22, ARL2BP, VCL, NRG1, SORBS2, TAGLN2, NID1, COL3A1, COL4A1, SMOX, SH2B3, ABCG5, MYO9B, FST, ARF5, HELLS, NUDT18, WFDC3, PDGFRB, SCD, SLC20A1, ST6GALNAC4, SGSM1, OTUD7B | 0.00114 |
| COL1A1 | 73 | 23 | COL4A2, NCAM1, FBLN2, COL6A3, GINS2, TMSB10, ITGBL1, COL3A1, GAS6, COL4A1, LOXL4, WT1, SERPINH1, IGFBP2, CD163, PDGFRB, EFEMP2, MMP12, CCDC3, TREM2, EGR2, PCOLCE, LOXL1 | 0.00114 |
| CXCL12 | Adipose (47); cardiac muscle (170); liver (30); muscle (36) | Adipose (10); cardiac muscle (54); liver (9); muscle (11) | Adipose (PODXL, MMP3, CXCL12, TRERF1, KDR, SLC6A6, MRVI1, KLK10, SLC22A3, RAB19); Cardiac_muscle (CAV2, PYGL, HLA-DRA, COL4A2, ZCCHC24, CTGF, CXCL12, PPAP2B, ST5, GRK5, AXL, LRP1, NID1, ZCCHC14, PECAM1, SNED1, FGFR1, EPS8, WIPF1, VPS13D, PTRF, HLA-B, CRISPLD2, TMEM176A, NR2F2, COL4A1, LIPA, ZHX3, NPR1, CXCL1, SLC24A3, SFRP2, RHOQ, LPAR1, MYLK, RAB13, SGK1, CD302, FTO, PRCP, USP25, TRIB2, ZBTB20, PSD3, TIMP3, WIPI1, PCOLCE, LTBP1, LAMB2, GUCY1A3, LAMC1, ANGPT1, NFIB, KLC1); Liver (PLEKHA1, CXCL12, COL6A3, SLC2A1, RERG, SLC6A6, CUX2, HSD17B12, SFTPB); Muscle (COL4A2, AHR, PODXL, CXCL12, S100Z, SCUBE3, BRPF1, RNF213, ARHGDIB, CNIH3, OR4X2) | Adipose (0.0534); cardiac muscle (0.0182); liver (0.00341); muscle (0.00114) |
| CFB | 20 | 10 | PLG, APOC1, C3, APOA5, C4B, APOF, HP, CFI, APOC2, APOA1 | 0.00114 |
| APOC2 | 27 | 10 | APOC1, SLC22A1, APOC3, APOA5, AGT, CYP4F12, ARG1, ABCG5, APOF, APOC2 | 0.00114 |
| RDH16 | Brain (43); muscle (36) | Brain (10); muscle (11) | Brain (APOC4, SLC22A1, APOC3, KLKB1, MBL1P, APOA5, APOF, PON1, AKR1C1, CFI); Muscle (PLG, SEC14L2, APOC3, HAAO, APOB, ABCG5, C8G, APOA4, GNMT, CYP2A13, F2) | Brain (0.0273); muscle (0.00114) |
| NGRN | 32 | 10 | HDDC3, TRIM68, FURIN, KLHL25, RCCD1, SPC24, SLC22A3, MESDC1, APOC2, AKAP13 | 0.00114 |
| FN1 | Kidney (16); PPI (75) | Kidney (3); PPI (21) | Kidney (ERBB4, ADAM12, FN1); PPI (COL4A2, FBLN2, COL4A3, ITGB6, CXCL12, FSTL3, MMP9, GALNT6, FN1, COL7A1, COL4A1, SDC2, FST, LPA, FASLG, COL4A4, SMAD9, MEP1B, LTBP1, IGFBP5, FBLN1) | Kidney (0.00114); PPI (0.0477) |
| NCOR2 | 12 | 7 | NCOR2, ACAD10, UBC, AACS, CUX2, PTPN11, VPS33A | 0.00114 |
The detailed information for all the KD genes is available in Table III in the online-only Data Supplement. CAD indicates coronary artery disease; GWAS, genome-wide association studies; KD, key driver; and PPI, protein–protein interaction.