Table 3.
Colocalization of Cytokine-Network-Associated Variants at the ABO and ZFPM2 Loci with Those of Plasma Protein Levels, Quantitative Traits, and Disease Risk
| Group/ Functions | Evidence | Names |
|---|---|---|
| ABO Locus (Chromosome 9) | ||
| Diseases | ||
| Cardiometabolic diseases | strong | pulmonary embolism, ischemic stroke, coronary artery disease, type 2 disease, |
| Cardiometabolic diseases | none | deep vein thrombosis |
| Blood Cell Traits | ||
| Blood cell counts | Strong | white blood cell, granulocytes, basophils + eosinophils, basophils + neutrophils, eosinophils + neutrophils, eosinophils, neutrophils, hematocrit (%), haemoglobin, myeloid, red blood cells, platelet distribution width |
| Blood cell counts | Suggestive | basophils, reticulocytes |
| Blood cell counts | None | monocyte, platelet, plateletcrit (%), red cell distribution width |
| Metabolites | ||
| IDL particle constituents | strong | Total cholesterol (IDL-C), free cholesterol (IDL-FC), total lipids (IDL-L), total particle concentration (IDL-P), phospholipids (IDL-PL), triglycerides (IDL-TG) |
| LDL subclass particle constituents | strong | For large particles: total cholesterol (L-LDL-C), cholesterol esters (L-LDL-CE), free cholesterol (L-LDL-FC), total lipids (L-LDL-L), total particle concentration (L-LDL-P), phospholipids (L-LDL-PL), For medium particles: total cholesterol (M-LDL-C), cholesterol esters (M-LDL-CE), total lipids (M-LDL-L), total particle concentration (M-LDL-P), phospholipids (M-LDL-PL) For small particles: total cholesterol (S-LDL-C), total lipids (S-LDL-L), total particle concentration (S-LDL-P) |
| VLDL subclass particle constituents | strong | For small particles: total cholesterol (S-VLDL-C), For extra-small particles: total lipids (XS-VLDL-L), phospholipids (XS-VLDL-PL) |
| Other | strong | HbA1c, Apolipoprotein B, total LDL cholesterol, total serum cholesterol |
| Proteins | ||
| Chemokine activity | strong | FAM3B, FAM3D, MIP-5, TECK, |
| Chemokine activity | suggestive | CCL28 |
| Chemokine receptors | strong | IL-3RA, HGF receptor, sGP130, VEGF-R2, VEGF-R3 |
| Chemokine receptors | none | TCCR |
| Receptor function and/or signaling | strong | F177A, GP116, IGF-1R, IR, JAG1, MBL, PEAR1, PYY, SECTM1, SEMA6A, TLR4 |
| Receptor function and/or signaling | suggestive | PLXB2 |
| Receptor function and/or signaling | none | CD109, CD209, GFRAL, GPIV, LIF-R, Notch-1, PEAR1, sTIE1, sTIE2 |
| Cell adhesion | strong | Cadherin-1, E-selectin, Endoglin, ICAM-4, ISLR2, Laminin, NCAM-L1, OX2G, P-selectin, sICAM-1, sICAM-2, sICAM-5 |
| Cell adhesion | none | ADAM23, BCAM, Cadherin-5, Desmoglein-2, ESAM |
| Enzyme function | strong | B3GN2, B4GT1, B4GT2, Cathepsin S, CLIC5, DPEP2, FA20B, FUT10, GLCE, GNS, IAP, LPH, MA1A2, NDST1, QSOX2, ST4S6, TPST2, XXLT1 |
| Enzyme function | none | ATS13, BGAT, CEL, CHSTB, DYR, MINP1, TLL1 |
| Miscellaneous | strong | C1GLC, CASC4, GOLM1, KIN17, THSD1, TUFT1, |
| Miscellaneous | none | Factor VIII, OBP2B |
| ZFPM2 Locus (Chromosome 8) | ||
| Blood Cell Traits | ||
| Blood cell counts | strong | white blood cells, granulocytes, basophils + neutrophils, neutrophils + eosinophils, basophils, neutrophils, myeloid, platelets, plateletcrit (%), platelet distribution width, mean platelet volume |
| Proteins | ||
| Cytokine/chemokine activity | strong | EDA, IL-7, PDGF-AA, PDGF-BB, PDGF-D, VEGF-A, NAP-2, RANTES, TARC |
| Immune response | strong | CLM2, COCH, CYTF, DB119 |
| Receptor function and/or signaling | strong | ANG-1, APP, BDNF, CD44, CGB2, CRIM1, Dkk-1, Dkk-4, EDAR, EPHB2, EPHB3, GI24, GRP, LIRB4, Mammaglobin-2, OBP2A, P2RX6, PAP1, PTPRD, RGS10, RGS3, RHOG, THA, MESD2 |
| Receptor function and/or signaling | suggestive | Ephrin-A3 |
| Receptor function and/or signaling | none | UNC5H4, sRAGE |
| Cell adhesion | strong | Galectin-7, KIRR2, MADCAM-1, MFGM, ON, P-Selectin, PCDG8, SCF, SPARCL1 |
| Enzyme activity | strong | Arylsulfatase A, ASM3A, B4GT7, Cathepsin A, CHSTB, CPXM1, FUT8, GSTM1-1, INP5E, MMEL2, MYSM1, PAI-1, PDIA5, RIFK, SIRT5, SPTC1, UD2A1 |
| Enzyme activity | none | PDE3A, ZFP91, LAML2, HECW1 |
| Enzyme inhibitor | strong | SERPINE2, SPINK5, TICN3, WFD13 |
| Transcription/translation | strong | APBB1, CENPW, HIF-1a, PAIP1 |
| Transcription/translation | suggestive | ID2 |
| Miscellaneous | strong | 4EBP2, APLP2, ARL1, ASIC4, CA063, Coactosin-like protein, CQ089, DJB11, MPP7, NSG2, PROL1, RBM28, SATB1, SYT11, SYT17, TXNDC4 |
| Miscellaneous | none | CNA2 |
Evidence: Evidence of colocalization, Strong = PP3+PP4 ≥ 0.99 and PP4/PP3 ≥ 5; Suggestive = PP3 + PP4 > 0.75 and PP4/PP3 > 3; None = association signal for the trait at the locus, but no evidence of colocalization
Refer to Table S9 for full descriptions of the proteins. The proteins have been grouped into broad functional categories using the Uniprot database.85