Table 1.
Pathways Enriched in Genes Associated with Nicotine Addiction.
| Pathways | P-value | PBH-value | Genes included |
|---|---|---|---|
| Neuroactive ligand-receptor interaction | 4.19 × 10−27 | 4.24 × 10−25 | ADRA2A, ADRB2, AGTR1, CHRM1, CHRM2, CHRM5, CHRNA1, CHRNA10, CHRNA2, CHRNA3, CHRNA4, CHRNA5, CHRNA6, CHRNA7, CHRNB1, CHRNB2, CHRNB3, CHRNB4, CHRND, CHRNG, CNR1, DRD1, DRD2, DRD3, DRD4, DRD5, GABBR1, GABBR2, GABRA2, GABRA4, GABRE, GALR1, GRIK1, GRIK2, GRIN1, GRIN2A, GRIN2B, GRIN3A, GRM7, HRH4, HTR1F, HTR2A, HTR6, NPY1R, NPY2R, NR3C1, OPRD1, OPRM1, PARD3 |
| Cocaine addiction | 2.10 × 10−16 | 1.06 × 10−14 | BDNF, CREB1, CREB5, DDC, DLG4, DRD1, DRD2, GNAS, GRIN1, GRIN2A, GRIN2B, GRIN3A, MAOA, MAOB, PPP1R1B, SLC18A2, SLC6A3, TH |
| Dopaminergic synapse | 4.12 × 10−12 | 1.39 × 10−10 | ARRB2, COMT, CREB1, CREB5, DDC, DRD1, DRD2, DRD3, DRD4, DRD5, GNAS, GRIN2A, GRIN2B, ITPR2, KCNJ6, MAOA, MAOB, PPP1R1B, PPP2R2B, SLC18A2, SLC6A3, TH |
| cAMP signaling pathway | 2.30 × 10−11 | 4.64 × 10−10 | ABCC4, ADRB2, BDNF, CAMK4, CHRM1, CHRM2, CREB1, CREB5, DRD1, DRD2, DRD5, GABBR1, GABBR2, GNAS, GRIN1, GRIN2A, GRIN2B, GRIN3A, HTR1F, HTR6, NPY, NPY1R, PDE4D, PPP1R1B, RAPGEF3, RHOA |
| Amphetamine addiction | 1.97 × 10−11 | 4.97 × 10−10 | CAMK4, CREB1, CREB5, DDC, DRD1, GNAS, GRIN1, GRIN2A, GRIN2B, GRIN3A, MAOA, MAOB, PPP1R1B, SLC18A2, SLC6A3, TH |
| Chemical carcinogenesis | 5.14 × 10−11 | 8.65 × 10−10 | ADH1B, CHRNA7, CYP1A1, CYP1B1, CYP2A6, CYP2E1, EPHX1, GSTM1, GSTM3, GSTP1, GSTT1, NAT1, NAT2, PTGS2, SULT1A1, UGT1A7, UGT2B10 |
| Drug metabolism | 3.07 × 10−9 | 4.42 × 10−8 | ADH1B, CYP2A6, CYP2B6, CYP2D6, CYP2E1, FMO1, GSTM1, GSTM3, GSTP1, GSTT1, MAOA, MAOB, UGT1A7, UGT2B10 |
| Nicotine addiction | 6.07 × 10−9 | 7.67 × 10−8 | CHRNA4, CHRNA6, CHRNA7, CHRNB2, GABRA2, GABRA4, GABRE, GRIN1, GRIN2A, GRIN2B, GRIN3A |
| Metabolism of xenobiotics by cytochrome P450 | 9.81 × 10−9 | 1.10 × 10−7 | ADH1B, CYP1A1, CYP1B1, CYP2A6, CYP2B6, CYP2D6, CYP2E1, EPHX1, GSTM1, GSTM3, GSTP1, GSTT1, UGT1A7, UGT2B10 |
| Alcoholism | 1.76 × 10−8 | 1.77 × 10−7 | BDNF, CAMK4, CREB1, CREB5, DDC, DRD1, DRD2, GNAS, GRIN1, GRIN2A, GRIN2B, GRIN3A, MAOA, MAOB, NPY, NTRK2, PPP1R1B, SHC3, SLC18A2, SLC6A3, TH |
| Cholinergic synapse | 4.92 × 10−8 | 4.52 × 10−7 | CAMK4, CHAT, CHRM1, CHRM2, CHRM5, CHRNA3, CHRNA4, CHRNA6, CHRNA7, CHRNB2, CHRNB4, CREB1, CREB5, ITPR2, KCNJ6, KCNQ3 |
| Serotonergic synapse | 5.60 × 10−8 | 4.72 × 10−7 | CYP2D6, DDC, GNAS, HTR1F, HTR2A, HTR6, ITPR2, KCNJ6, MAOA, MAOB, PTGS2, RAPGEF3, SLC18A2, SLC6A4, TPH1, TPH2 |
| Morphine addiction | 1.04 × 10−6 | 8.05 × 10−6 | ARRB1, ARRB2, DRD1, GABBR1, GABBR2, GABRA2, GABRA4, GABRE, GNAS, KCNJ6, OPRM1, PDE1C, PDE4D |
| Calcium signaling pathway | 1.81 × 10−6 | 1.30 × 10−5 | ADRB2, AGTR1, CAMK4, CHRM1, CHRM2, CHRM5, CHRNA7, DRD1, DRD5, GNAS, GRIN1, GRIN2A, HTR2A, HTR6, ITPR2, NOS2, NOS3, PDE1C |
| Tryptophan metabolism | 1.04 × 10−5 | 7.03 × 10−5 | ALDH2, CYP1A1, CYP1B1, DDC, MAOA, MAOB, TPH1, TPH2 |
| Glutamatergic synapse | 1.34 × 10−5 | 8.47 × 10−5 | DLG4, GNAS, GRIK1, GRIK2, GRIN1, GRIN2A, GRIN2B, GRIN3A, GRM7, HOMER1, HOMER2, ITPR2, SLC1A2 |
| Tyrosine metabolism | 3.80 × 10−5 | 2.13 × 10−4 | ADH1B, COMT, DBH, DDC, MAOA, MAOB, TH |
| Estrogen signaling pathway | 8.00 × 10−5 | 4.25 × 10−4 | CREB1, CREB5, ESR1, GABBR1, GABBR2, GNAS, ITPR2, KCNJ6, NOS3, OPRM1, SHC3 |
| Rap1 signaling pathway | 6.87 × 10−4 | 3.31 × 10−3 | CNR1, DRD2, FGF12, FGF14, GNAS, GRIN1, GRIN2A, GRIN2B, ITGB3, MAGI1, PARD3, RAPGEF3, RHOA, SIPA1L2, TEK |
| Steroid hormone biosynthesis | 9.95 × 10−4 | 4.37 × 10−3 | COMT, CYP17A1, CYP1A1, CYP1B1, CYP2E1, UGT1A7, UGT2B10 |