Table 2.
Over-represented (p<0.05) canonical pathways in which RA and SLE overlapping loci, RA only loci and SLE only loci are involved
| Canonical pathway | Type of pathway | p Value | Genes in pathway |
|---|---|---|---|
| SLE/RA overlap | |||
| Dendritic cell maturation | Cellular immune response, cytokine signalling, pathogen-influenced signalling | 1.4×10−4 | STAT4, FCGR2A, HLA-DRB1 |
| T helper cell differentiation | Cellular immune response, cytokine signalling | 9.8×10−4 | STAT4, HLA-DRB1 |
| CTLA4 signalling in cytotoxic T lymphocytes | Cellular immune response | 1.8×10−3 | HLA-DRB1, PTPN22 |
| Role of NFAT in regulation of the immune response | Cellular immune response, humoral immune response, intracellular and second messenger signalling | 6.2×10−3 | FCGR2A, HLA-DRB1 |
| TNFR2 signalling | Apoptosis, cytokine signalling | 0.02 | TNFAIP3 |
| B-cell development | Cellular growth, proliferation and development, humoral immune response | 0.02 | HLA-DRB1 |
| Antigen presentation pathway | Cellular immune response, humoral immune response | 0.03 | HLA-DRB1 |
| Allograft rejection signalling | Cellular immune response, disease specific pathway | 0.03 | HLA-DRB1 |
| Autoimmune thyroid disease signalling | Cellular immune response, disease specific pathway, humoral immune response | 0.03 | HLA-DRB1 |
| Graft-versus-host disease signalling | Cellular immune response, disease specific pathway | 0.03 | HLA-DRB1 |
| TNFR1 signalling | Apoptosis, cytokine signalling | 0.03 | TNFAIP3 |
| Nur77 signalling in T lymphocytes | Apoptosis, cellular immune response, Nuclear receptor signalling | 0.04 | HLA-DRB1 |
| Calcium-induced T lymphocyte apoptosis | Apoptosis, cellular immune response | 0.04 | HLA-DRB1 |
| CD40 signalling | Cellular immune response, humoral immune response | 0.04 | TNFAIP3 |
| IL-10 signalling | Cellular immune response, cytokine signalling | 0.04 | FCGR2A |
| JAK/Stat signalling | Apoptosis, cellular growth, proliferation and development, intracellular and second messenger signalling | 0.04 | STAT4 |
| RA only | |||
| iCOS-iCOSL signalling in T helper cells | Cellular immune response | 9.8×10−9 | PTPRC, CD28, PRKCQ, CD40, IL2RA, IL2RB |
| T helper cell differentiation | Cellular immune response, cytokine signalling | 5.2×10−8 | IL21, IL6ST, CD28, CD40, IL2RA |
| Altered T-cell and B-cell signalling in RA | Cellular immune response, disease-specific pathways | 6.6×10−6 | IL21, CD28, CD40, CCL21 |
| T-cell receptor signalling | Cellular immune response | 1.3×10−5 | PTPRC, CD28, PRKCQ, CTLA4 |
| IL-12 signalling and production in macrophages | Cellular immune response, cytokine signalling | 2.0×10−5 | TRAF6, PRKCQ, CD40, REL |
| CD28 signalling in T helper cells | Cellular immune response | 2.7×10−5 | PTPRC, CD28, PRKCQ, CTLA4 |
| CD40 signalling | Cellular immune response, humoral immune response | 1.0×10−4 | TRAF6, CD40, TRAF1 |
| Cross-talk between dendritic cells and natural killer cells | Cellular immune response | 3.7×10−4 | CD28, CD40, IL2RB |
| B cell development | Cellular growth, proliferation and development, humoral immune response | 9.3×10−4 | PTPRC, CD40 |
| Systemic lupus erythematosus signalling | Disease-specific pathways | 1.0×10−3 | PTPRC, CD28, CD40 |
| Role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis | Disease-specific pathways | 1.2×10−3 | TRAF6, IL6ST, PRKCQ, TRAF1 |
| NF-κB signalling | Cellular immune response, cytokine signalling, humoral immune response, organismal growth and development | 1.3×10−3 | TRAF6, PRKCQ, CD40 |
| April -mediated signalling | Apoptosis | 1.5×10−3 | TRAF6, TRAF1 |
| Dendritic cell maturation | Cellular immune response, cytokine signalling, pathogen-influenced signalling | 1.6×10−3 | TRAF6, CD40, CD58 |
| B-cell activating factor signalling | Cellular growth, proliferation and development, humoral immune response | 1.7×10−3 | TRAF6, TRAF1 |
| Allograft rejection signalling | Cellular immune response, disease-specific pathways | 1.8×10−3 | CD28, CD40 |
| Autoimmune thyroid disease signalling | Cellular immune response, disease-specific pathways, humoral immune response | 1.9×10−3 | CD28, CD40 |
| Primary immunodeficiency signalling | Cellular immune response, disease-specific pathways, humoral immune response | 2.3×10−3 | PTPRC, CD40 |
| IL-2 signalling | Cellular immune response, cytokine signalling | 3.1×10−3 | IL2RA, IL2RB |
| Lymphotoxin β receptor signalling | Apoptosis | 3.2×10−3 | TRAF6, TRAF1 |
| Activation of IRF by cytosolic pattern recognition receptors | Cellular immune response | 4.1×10−3 | TRAF6, CD40 |
| Small cell lung cancer signalling | Cancer, disease-specific pathways | 5.5×10−3 | TRAF6, TRAF1 |
| Communication between innate and adaptive immune cells | Cellular immune response | 5.8×10−3 | CD28, CD40 |
| IL-6 signalling | Cellular immune response, cytokine signalling | 8.1×10−3 | TRAF6, IL6ST |
| CTLA4 aignalling in cytotoxic T lymphocytes | Cellular immune response | 8.7×10−3 | CD28, CTLA4 |
| Type I diabetes mellitus signalling | Apoptosis, disease-specific pathways, | 0.01 | TRAF6, CD28 |
| PKC signalling in T lymphocytes | Cellular immune response | 0.01 | CD28, PRKCQ |
| Hepatic fibrosis/hepatic stellate cell activation | Disease-specific pathways | 0.02 | CD40, CCL21 |
| Hepatic cholestasis | Disease-specific pathways | 0.02 | TRAF6, PRKCQ |
| B cell receptor signalling | Humoral immune response | 0.02 | PTPRC, PRKCQ |
| IL-8 signalling | Cellular immune response, cytokine signalling | 0.03 | TRAF6, PRKCQ |
| Acute phase response signalling | Cytokine signalling | 0.03 | TRAF6, IL6ST |
| Role of NFAT in regulation of the immune response | Cellular immune response, humoral immune response, intracellular and second messenger signalling | 0.03 | CD28, PRKCQ |
| Role of NFAT in cardiac hypertrophy | Cardiovascular signalling, disease-specific pathways | 0.03 | IL6ST, PRKCQ |
| TNFR2 signalling | Apoptosis, cytokine signalling | 0.04 | TRAF1 |
| 4-1BB signalling in T lymphocytes | Cellular immune response | 0.04 | TRAF1 |
| SLE only | |||
| Mitotic roles of polo-like kinase | Cell cycle regulation | 0.035 | PTTG1 |
| Angiopoietin signalling | Cardiovascular signalling, cellular growth, proliferation and development, growth factor signalling | 0.041 | TNIP1 |
| Ubiquinone biosynthesis | Metabolism of cofactors and vitamins | 0.045 | UHRF1BP1 |
| Caveolar-mediated endocytosis signalling | Cellular immune response, organismal growth and development, pathogen-influenced signalling | 0.046 | ITGAM |
NFAT, nuclear factor of activated T cells; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus.