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Table 1 Pathways enriched in Alzgseta

From: Analyzing the genes related to Alzheimer’s disease via a network and pathway-based approach

Pathway p valueb p BH valuec Genes included in the pathwayd
Cytokines and inflammatory response 1.03 × 10–9 8.79 × 10–8 CXCL8, HLA-DRA, HLA-DRB1, IL10, IL12A, IL12B, IL1A, IL4, IL6, TGFB1, TNF
cytokine network 9.89 × 10–9 3.84 × 10–7 CXCL8, IL10, IL12A, IL12B, IL18, IL1A, IL4, IL6, TNF
Hematopoietic cell lineage 1.92 × 10–7 5.46 × 10–6 CD14, CD33, CD36, CD44, CR1, HLA-DRA, HLA-DRB1, HLA-DRB5, IL1A, IL1B, IL4, IL6, IL6R, MME, TNF
Dendritic cells in regulating TH1 and TH2 Development 3.11 × 10–7 8.29 × 10–6 CD33, IL10, IL12A, IL12B, IL4, TLR2, TLR4, TLR9
Ovarian steroidogenesis 5.88 × 10–6 1.09 × 10–4 ALOX5, CYP19A1, FSHR, IGF1, INS, LDLR, LHCGR, PLA2G4A, PTGS2, STAR
IL-5 signaling pathway 9.00 × 10–6 1.60 × 10–4 HLA-DRA, HLA-DRB1, IL1B, IL4, IL6
Neurotrophin signaling pathway 1.08 × 10–5 1.77 × 10–4 BDNF, CAMK2D, GSK3B, IRS1, NGF, NGFR, NTF3, NTRK1, NTRK2, PIK3R1, PSEN1, PSEN2, SOS2, TP53, TP73
HIF-1 signaling pathway 1.12 × 10–5 1.77 × 10–4 CAMK2D, EIF4EBP1, GAPDH, HMOX1, IGF1, IL6, IL6R, INS, NOS3, PIK3R1, RPS6KB2, TF, TLR4, VEGFA
NOD-like receptor signaling pathway 1.66 × 10–5 2.37 × 10–4 CARD8, CCL2, CXCL8, IL18, IL1B, IL6, MEFV, NLRP1, NLRP3, TNF
Mechanism of gene regulation by peroxisome proliferators via PPARα 1.95 × 10–5 2.69 × 10–4 APOA1, CD36, INS, LPL, PIK3R1, PPARA, PTGS2, RXRA, SP1, TNF
Th1/Th2 differentiation 2.54 × 10–5 3.19 × 10–4 HLA-DRA, HLA-DRB1, IL12A, IL12B, IL18, IL4
Antigen-dependent B-cell activation 2.68 × 10–5 3.26 × 10–4 FAS, HLA-DRA, HLA-DRB1, IL10, IL4
Oxidative phosphorylation 3.74 × 10–5 4.39 × 10–4 COX10, COX15, MT-ATP6, MT-ATP8, MT-CO1, MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L, MT-ND5, MT-ND6
PI3K-Akt signaling pathway 3.80 × 10–5 4.39 × 10–4 COL11A1, EFNA5, EIF4EBP1, FGF1, GNB3, GSK3B, IGF1, IL4, IL6, IL6R, INS, IRS1, NGF, NGFR, NOS3, PCK1, PIK3R1, PPP2R2B, RELN, RPS6KB2, RXRA, SOS2, TLR2, TLR4, TP53, VEGFA, YWHAQ
NF-κB signaling pathway 4.83 × 10–5 5.42 × 10–4 CD14, CXCL8, ICAM1, IL1B, LCK, PARP1, PLAU, PTGS2, TLR4, TNF, TRAF2, UBE2I
Phagosome 7.77 × 10–5 8.29 × 10–4 CD14, CD36, CTSS, HLA-A, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5, MBL2, MPO, NOS1, OLR1, RAB7A, TAP2, TLR2, TLR4
Erythrocyte differentiation pathway 9.33 × 10–5 9.49 × 10–4 CCL3, IGF1, IL1A, IL6, TGFB1
IL-10 anti-inflammatory signaling pathway 1.82 × 10–4 1.69 × 10–3 HMOX1, IL10, IL1A, IL6, TNF
Cells and molecules involved in local acute inflammatory response 1.82 × 10–4 1.69 × 10–3 CXCL8, ICAM1, IL1A, IL6, TNF
Toll-like receptor signaling pathway 2.15 × 10–4 1.95 × 10–3 CCL3, CD14, CXCL8, IL12A, IL12B, IL1B, IL6, PIK3R1, TLR2, TLR4, TLR9, TNF
Free radical induced apoptosis 2.22 × 10–4 1.97 × 10–3 CXCL8, GPX1, SOD1, TNF
Intestinal immune network for IgA production 2.65 × 10–4 2.26 × 10–3 HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5, IL10, IL4, IL6, TGFB1
Selective expression of chemokine receptors during T-cell polarization 3.35 × 10–4 2.68 × 10–3 CCL3, CCR2, IL12A, IL12B, IL4, TGFB1
B lymphocyte cell surface molecules 3.39 × 10–4 2.68 × 10–3 CR1, HLA-DRA, HLA-DRB1, ICAM1
Phosphorylation of MEK1 by cdk5/p35 downregulates the MAP kinase pathway 3.39 × 10–4 2.68 × 10–3 CDK5, CDK5R1, NGF, NGFR
Complement and coagulation cascades 4.61 × 10–4 3.58 × 10–3 A2M, C4A, C4B, CFH, CR1, F13A1, MBL2, PLAU, SERPINA1
ABC transporters 5.87 × 10–4 4.32 × 10–3 ABCA1, ABCA2, ABCA7, ABCC2, ABCG1, ABCG2, TAP2
Signal transduction through IL-1R 6.97 × 10–4 5.05 × 10–3 IL1A, IL1B, IL1RN, IL6, TGFB1, TNF
mTOR signaling pathway 8.19 × 10–4 5.83 × 10–3 EIF4EBP1, IGF1, INS, IRS1, PIK3R1, RPS6KB2, TNF, VEGFA
Adhesion and diapedesis of granulocytes 9.49 × 10–4 6.65 × 10–3 CXCL8, ICAM1, IL1A, TNF
TNF signaling pathway 1.12 × 10–3 7.69 × 10–3 CCL2, FAS, ICAM1, IL1B, IL6, MAGI2, MMP3, PIK3R1, PTGS2, TNF, TRAF2
MAPK signaling pathway 1.13 × 10–3 7.69 × 10–3 BDNF, CD14, FAS, FGF1, IL1A, IL1B, MAPK8IP1, MAPT, MEF2C, NGF, NTF3, NTRK1, NTRK2, PLA2G4A, SOS2, TGFB1, TNF, TP53, TRAF2
The IGF-1 receptor and longevity 1.26 × 10–3 8.28 × 10–3 IGF1, PIK3R1, SOD1, SOD2
Glutathione metabolism 1.45 × 10–3 8.95 × 10–3 GPX1, GSTM1, GSTM3, GSTO1, GSTO2, GSTP1, GSTT1
Cytokine–cytokine receptor interaction 1.48 × 10–3 8.95 × 10–3 CCL2, CCL3, CCR2, CXCL8, FAS, IL10, IL12A, IL12B, IL18, IL1A, IL1B, IL23R, IL4, IL6, IL6R, NGFR, TGFB1, TNF, VEGFA
Serotonergic synapse 1.50 × 10–3 8.95 × 10–3 ALOX5, APP, CYP2D6, GNB3, HTR2A, HTR6, KCNJ6, MAOA, PLA2G4A, PTGS2, SLC6A4
Antigen processing and presentation 1.63 × 10–3 9.53 × 10–3 CTSS, HLA-A, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5, HSPA5, TAP2, TNF
Drug metabolism—cytochrome P450 1.88 × 10–3 1.05 × 10–2 CYP2D6, GSTM1, GSTM3, GSTO1, GSTO2, GSTP1, GSTT1, MAOA
Cell cycle: G1/S check point 2.13 × 10–3 1.18 × 10–2 CDK1, CDKN2A, GSK3B, TGFB1, TP53
Fcε RI signaling pathway 2.26 × 10–3 1.23 × 10–2 FCER1G, GAB2, IL4, INPP5D, PIK3R1, PLA2G4A, SOS2, TNF
Apoptosis 2.28 × 10–3 1.23 × 10–2 FAS, IL1A, IL1B, NGF, NTRK1, PIK3R1, TNF, TP53, TRAF2
Role of Erk5 in neuronal survival 2.61 × 10–3 1.39 × 10–2 MEF2A, MEF2C, NTRK1, PIK3R1
Bioactive peptide-induced signaling pathway 2.90 × 10–3 1.52 × 10–2 CAMK2D, CDK5, GNA11, MAPT, MYLK, PTK2B
Control of skeletal myogenesis by HDAC and calcium/calmodulin-dependent kinase (CaMK) 2.93 × 10–3 1.52 × 10–2 IGF1, INS, MEF2A, MEF2C, PIK3R1
Metabolism of xenobiotics by cytochrome P450 3.22 × 10–3 1.62 × 10–2 CYP2D6, GSTM1, GSTM3, GSTO1, GSTO2, GSTP1, GSTT1, HSD11B1
Ras-independent pathway in NK cell-mediated cytotoxicity 3.92 × 10–3 1.88 × 10–2 HLA-A, IL18, PIK3R1, PTK2B
Dopaminergic synapse 4.48 × 10–3 2.11 × 10–2 CAMK2D, CLOCK, COMT, DRD4, GNB3, GRIN2B, GSK3B, KCNJ6, MAOA, PPP2R2B, SLC6A3
Cholinergic synapse 4.57 × 10–3 2.12 × 10–2 CAMK2D, CHAT, CHRNA3, CHRNA4, CHRNA7, CHRNB2, GNA11, GNB3, KCNJ6, PIK3R1
The co-stimulatory signal during T-cell activation 4.72 × 10–3 2.17 × 10–2 HLA-DRA, HLA-DRB1, LCK, PIK3R1
Adhesion and diapedesis of lymphocytes 5.03 × 10–3 2.28 × 10–2 CXCL8, ICAM1, IL1A
Notch signaling pathway 5.07 × 10–3 2.28 × 10–2 APH1A, APH1B, NCSTN, PSEN1, PSEN2, PSENEN
Role of ERBB2 in signal transduction and oncology 5.61 × 10–3 2.50 × 10–2 ESR1, IL6, IL6R, PIK3R1
Aminoacyl-tRNA biosynthesis 6.37 × 10–3 2.80 × 10–2 MT-TG, MT-TH, MT-TL2, MT-TQ, MT-TR, MT-TS2, MT-TT
Trka receptor signaling pathway 6.55 × 10–3 2.80 × 10–2 NGF, NTRK1, PIK3R1
Rac 1 cell motility signaling pathway 6.62 × 10–3 2.80 × 10–2 CDK5, CDK5R1, MYLK, PIK3R1
CTCF: first multivalent nuclear factor 6.62 × 10–3 2.80 × 10–2 CDKN2A, PIK3R1, TGFB1, TP53
Regulation of PGC-1a 7.74 × 10–3 3.21 × 10–2 CAMK2D, MEF2A, MEF2C, PPARA
Calcium signaling pathway 7.85 × 10–3 3.22 × 10–2 ADRB1, ADRB2, ADRB3, CAMK2D, CHRNA7, GNA11, HTR2A, HTR6, LHCGR, MYLK, NOS1, NOS3, PTK2B
Lck and Fyn tyrosine kinases in initiation of TCR activation 8.30 × 10–3 3.38 × 10–2 HLA-DRA, HLA-DRB1, LCK
Adipocytokine signaling pathway 8.75 × 10–3 3.52 × 10–2 CD36, IRS1, PCK1, PPARA, RXRA, TNF, TRAF2
Ras signaling pathway 9.43 × 10–3 3.76 × 10–2 EFNA5, EXOC2, FGF1, GAB2, GNB3, GRIN2B, IGF1, INS, NGF, NGFR, PIK3R1, PLA2G3, PLA2G4A, SOS2, VEGFA
Prolactin signaling pathway 1.02 × 10–2 3.96 × 10–2 ESR1, ESR2, GSK3B, INS, LHCGR, PIK3R1, SOS2
Catecholamine biosynthesis, tyrosine → dopamine → noradrenaline → adrenaline 1.05 × 10–2 3.99 × 10–2 DBH, PNMT
Fat digestion and absorption 1.14 × 10–2 4.32 × 10–2 ABCA1, APOA1, APOA4, CD36, PLA2G3
Stress induction of HSP regulation 1.26 × 10–2 4.63 × 10–2 FAS, IL1A, TNF
Regulation of hematopoiesis by cytokines 1.26 × 10–2 4.63 × 10–2 CXCL8, IL4, IL6
CTL-mediated immune response against target cells 1.26 × 10–2 4.63 × 10–2 FAS, HLA-A, ICAM1
Osteoclast differentiation 1.32 × 10–2 4.81 × 10–2 GAB2, IL1A, IL1B, LCK, PIK3R1, PPARG, TGFB1, TNF, TRAF2, TREM2
  1. aAlzheimer’s disease-related genes gene set
  2. bCalculated by Fisher’s exact test
  3. cAdjusted by the Benjamini and Hochberg (BH) method
  4. dGenes among Alzgset included in the specific pathway