Table 4.
Top pathways showing the association of height with diseases
| Disease | Pathway | Height-associated genes in the pathway | Number of genes | Odds ratio | p value | Rank of height pathway# |
|---|---|---|---|---|---|---|
| Coronary artery diseases (CAD) | Caveolar-mediated endocytosis signalling | FLNB, COPA, COPB1, INSR, ITGB8, HLA-C | 6 | 0.50 | < 0.001 | 189 |
| CAD | Production of nitric oxide and reactive oxygen species in macrophages | FGFR2, PIK3R3, PIK3C2A, RHOD, PIK3R1, NFKBIA, MAP2K4, FRS2, GRB2, CREBBP, FGFR4, PRKCZ, MAP3K3 | 13 | 0.65 | < 0.001 | 159 |
| CAD | Dendritic cell maturation | FGFR2, COL10A1, PIK3R3, PIK3C2A, PIK3R1, NFKBIA, CREB5, MAP2K4, FRS2, GRB2, HLA-C, CREBBP, TAB1, COL11A2, FGFR4 | 15 | 0.66 | < 0.001 | 106 |
| CAD | NGF signalling | FGFR2, PIK3R3, PIK3C2A, RAF1, PIK3R1, TP53, CREB5, MAP2K4, FRS2, GRB2, CREBBP, FGFR4, PRKCZ, MAP3K3 | 14 | 0.67 | < 0.001 | 45 |
| CAD | Germ cell-sertoli cell junction signalling | FGFR2, PIK3R3, PIK3C2A, CTNNB1, RHOD, TGFB2, FER, PIK3R1, MAP2K4, FRS2, GRB2, FGFR4, MAP3K3 | 13 | 0.69 | < 0.001 | 135 |
| Hypertension | Hepatic cholestasis | MAP2K4, TGFB2, RXRA, INSR, SLCO1C1, FGFR4, PRKCZ, NFKBIA, ESR1, ADCY9 | 10 | 0.58 | < 0.001 | 186 |
| Hypertension | RAR activation | PML, PIK3R3, NCOA1, TGFB2, SMAD6, NSD1, BMP2, PIK3R1, SMAD7, RDH14, MAP2K4, SMAD3, RXRA, CREBBP, IGFBP3, PRKCZ, ADCY9 | 17 | 0.75 | < 0.001 | 59 |
| Hypertension | IL-1 signalling | GNAS, MAP2K4, GNA12, TAB1, NFKBIA, ADCY9 | 6 | 0.57 | < 0.001 | 200 |
| Hypertension | TGF-β signalling | SMAD7, MAP2K4, SMAD3, RAF1, TGFB2, GRB2, SMAD6, CREBBP, TAB1, BMP2, RUNX2 | 11 | 0.75 | 0.001 | 64 |
| Hypertension | Dopamine-DARPP32 feedback in cAMP signalling | GNAS, ITPR3, CREB5, PRKG1, PRKG2, ITPR1, KCNJ15, KCNJ12, CREBBP, KCNJ16, PRKCZ, ADCY9 | 12 | 0.74 | 0.001 | 150 |
| Atrial fibrillation | ERK5 signalling | CREB5, GNA12, CREBBP, PRKCZ, MAP3K3, MEF2C, FOXO3 | 7 | 1.83 | < 0.001 | 154 |
| Atrial fibrillation | Wnt/β-catenin signalling | LRP5, SOX8, CTNNB1, WNT5A, SOX5, TGFB2, TP53, AXIN2, TLE3, SFRP4, SOX9, CREBBP, TAB1, WNT4 | 14 | 1.68 | < 0.001 | 107 |
| Atrial fibrillation | Androgen signalling | GNAS, NCOA1, POLR2A, SMAD3, GNA12, CREBBP, PRKCZ | 7 | 2.14 | 0.001 | 197 |
| Atrial fibrillation | Role of Oct4 in mammalian embryonic stem cell pluripotency | REST, FAM208A, RB1, WWP2, TP53, CCNF | 6 | 1.90 | 0.004 | 146 |
| Atrial fibrillation | Growth hormone signalling | FGFR2, SOCS5, PIK3R3, PIK3C2A, SOCS2, PIK3R1, IGF2, IGF1R, FRS2, GHR, GRB2, IGFBP3, FGFR4, PRKCZ | 14 | 1.39 | 0.006 | 9 |
| Venous thromboembolism (VTE) | Synaptic long-term depression | IGF1R, GNAS, ITPR3, RAF1, PRKG1, GNA12, PRKG2, ITPR1, PRKCZ | 9 | 1.75 | < 0.001 | 192 |
| VTE | Glioma signalling | FGFR2, MTOR, PIK3R3, PIK3C2A, RBL2, RAF1, PIK3R1, TP53, IGF2, IGF1R, FRS2, GRB2, RBL1, CDK6, FGFR4, RB1, PRKCZ | 17 | 1.59 | < 0.001 | 5 |
| VTE | Role of tissue factor in cancer | FGFR2, MTOR, PIK3R3, PIK3C2A, FRS2, GNA12, GRB2, PIK3R1, FGFR4, TP53 | 10 | 1.69 | < 0.001 | 155 |
| VTE | Molecular mechanisms of cancer | FGFR2, LRP5, PIK3C2A, PTCH1, WNT5A, RHOD, ARHGEF12, GNA12, SMAD6, BMP2, PIK3R1, MAX, NFKBIA, TP53, CCND3, SMAD7, FRS2, SMAD3, GRB2, BMP6, CREBBP, RBL1, CDK6, FGFR4, PRKCZ, PIK3R3, IHH, CTNNB1, RAF1, TGFB2, GNAS, MAP2K4, TAB1, WNT4, RB1, ADCY9 | 36 | 1.37 | < 0.001 | 1 |
| VTE | Role of NFAT in regulation of the immune response | FGFR2, NFATC4, PIK3R3, PIK3C2A, RAF1, GNA12, PIK3R1, NFATC1, NFKBIA, MEF2C, NFATC3, GNAS, ITPR3, FRS2, GRB2, ITPR1, FGFR4, ZAP70 | 18 | 1.51 | < 0.001 | 41 |
| Intervertebral disc disorder (IDD) | Protein kinase A signalling | FLNB, AKAP13, PTCH1, HIST1H1E, NFKBIA, PDE11A, SMAD3, ITPR1, PDE3A, CREBBP, PTPDC1, PRKCZ, NFATC4, PTPN14, IHH, CTNNB1, RAF1, TGFB2, NFATC1, ANAPC10, NFATC3, GNAS, ITPR3, CREB5, PTPRG, CDC16, ADCY9, PDE1A | 28 | 1.31 | 0.005 | 42 |
| IDD | Wnt/β-catenin signalling | LRP5, SOX8, CTNNB1, WNT5A, SOX5, TGFB2, TP53, AXIN2, TLE3, SFRP4, SOX9, CREBBP, TAB1, WNT4 | 14 | 1.49 | 0.009 | 107 |
| IDD | PI3K signalling in B lymphocytes | NFATC3, NFATC4, ITPR3, RAF1, PLEKHA1, ITPR1, PIK3R1, NFATC1, PRKCZ, NFKBIA, FOXO3 | 11 | 1.80 | 0.022 | 132 |
| IDD | VDR/RXR activation | LRP5, NCOA1, TGFB2, RXRA, IGFBP3, PRKCZ, RUNX2 | 7 | 1.52 | 0.023 | 174 |
| IDD | Factors promoting cardiogenesis in vertebrates | LRP5, CTNNB1, TGFB2, BMP6, BMP2, PRKCZ, MEF2C | 7 | 1.95 | 0.027 | 187 |
| Hip fracture | Actin cytoskeleton signalling | FGFR2, PIK3R3, PIK3C2A, SLC9A1, RAF1, ARHGEF12, GNA12, FGF18, PIK3R1, FN1, FRS2, GRB2, FGFR4, SSH2 | 14 | 3.46 | < 0.001 | 166 |
| Hip fracture | SAPK/JNK signalling | FGFR2, PIK3R3, PIK3C2A, GNA12, PIK3R1, NFATC1, TP53, NFATC3, MAP2K4, FRS2, GRB2, TAB1, FGFR4, MAP3K3 | 14 | 2.56 | < 0.001 | 20 |
| Hip fracture | NRF2-mediated oxidative stress response | FGFR2, FKBP5, PIK3R3, PIK3C2A, MAP2K4, FRS2, RAF1, GRB2, CREBBP, PIK3R1, FGFR4, PRKCZ | 12 | 3.18 | 0.002 | 176 |
| Hip fracture | Glucocorticoid receptor signalling | FGFR2, NFATC4, PIK3R3, NCOA1, PIK3C2A, POLR2A, RAF1, TGFB2, PIK3R1, NFATC1, NFKBIA, NFATC3, FKBP5, MAP2K4, FRS2, SMAD3, GRB2, CREBBP, TAB1, FGFR4, ESR1, FOXO3, PRKAB2 | 23 | 2.18 | 0.002 | 43 |
| Hip fracture | Signalling by rho family GTPases | FGFR2, PIK3R3, PIK3C2A, SLC9A1, RHOD, RAF1, ARHGEF12, GNA12, PIK3R1, GNAS, MAP2K4, FRS2, GRB2, CDC42EP3, FGFR4, PRKCZ | 16 | 2.31 | 0.003 | 141 |
| Diaphragmatic hernia | ERK5 signalling | CREB5, GNA12, CREBBP, PRKCZ, MAP3K3, MEF2C, FOXO3 | 7 | 0.78 | 0.013 | 154 |
| Diaphragmatic hernia | Protein kinase A signalling | FLNB, AKAP13, PTCH1, HIST1H1E, NFKBIA, PDE11A, SMAD3, ITPR1, PDE3A, CREBBP, PTPDC1, PRKCZ, NFATC4, PTPN14, IHH, CTNNB1, RAF1, TGFB2, NFATC1, ANAPC10, NFATC3, GNAS, ITPR3, CREB5, PTPRG, CDC16, ADCY9, PDE1A | 28 | 0.85 | 0.015 | 42 |
| Diaphragmatic hernia | Androgen signalling | GNAS, NCOA1, POLR2A, SMAD3, GNA12, CREBBP, PRKCZ | 7 | 0.77 | 0.015 | 197 |
| Diaphragmatic hernia | GPCR-mediated integration of enteroendocrine signalling exemplified by an L cell | GNAS, ITPR3, ITPR1, GALR1, ADCY9 | 5 | 0.63 | 0.018 | 201 |
| Diaphragmatic hernia | SUMOylation pathway | SENP3, RFC1, PML, CTBP2, MAP2K4, RHOD, SENP6, SP3, CREBBP, NFKBIA, TP53 | 11 | 0.77 | 0.025 | 77 |
| Gastro-oesophageal reflux disease (GORD) | Virus entry via endocytic pathways | FGFR2, FLNB, PIK3R3, PIK3C2A, FRS2, GRB2, ITGB8, HLA-C, PIK3R1, FGFR4, PRKCZ | 11 | 0.69 | 0.013 | 90 |
| GORD | HER-2 signalling in breast cancer | FGFR2, PIK3R3, PIK3C2A, FRS2, GRB2, ITGB8, CDK6, PIK3R1, FGFR4, PRKCZ, TP53 | 11 | 0.81 | 0.015 | 69 |
| GORD | Role of Oct4 in mammalian embryonic stem cell pluripotency | REST, FAM208A, RB1, WWP2, TP53, CCNF | 6 | 0.71 | 0.018 | 146 |
| GORD | mTOR signalling | RPS27L, FGFR2, MTOR, PIK3R3, PIK3C2A, RHOD, INSR, PIK3R1, FRS2, GRB2, EIF3H, MLST8, FGFR4, PRKCZ, PRKAB2 | 15 | 0.81 | 0.020 | 115 |
| GORD | eNOS signalling | FGFR2, LPAR1, PIK3R3, SLC7A1, PIK3C2A, PRKG1, PIK3R1, GNAS, ITPR3, FRS2, GRB2, ITPR1, CCNA2, FGFR4, PRKCZ, ESR1, ADCY9, PRKAB2 | 18 | 0.83 | 0.024 | 18 |
| Vasculitis | Glioma signalling | FGFR2, MTOR, PIK3R3, PIK3C2A, RBL2, RAF1, PIK3R1, TP53, IGF2, IGF1R, FRS2, GRB2, RBL1, CDK6, FGFR4, RB1, PRKCZ | 17 | 1.82 | < 0.001 | 5 |
| Vasculitis | Molecular mechanisms of cancer | FGFR2, LRP5, PIK3C2A, PTCH1, WNT5A, RHOD, ARHGEF12, GNA12, SMAD6, BMP2, PIK3R1, MAX, NFKBIA, TP53, CCND3, SMAD7, FRS2, SMAD3, GRB2, BMP6, CREBBP, RBL1, CDK6, FGFR4, PRKCZ, PIK3R3, IHH, CTNNB1, RAF1, TGFB2, GNAS, MAP2K4, TAB1, WNT4, RB1, ADCY9 | 36 | 1.52 | 0.002 | 1 |
| Vasculitis | Growth hormone signalling | FGFR2, SOCS5, PIK3R3, PIK3C2A, SOCS2, PIK3R1, IGF2, IGF1R, FRS2, GHR, GRB2, IGFBP3, FGFR4, PRKCZ | 14 | 1.71 | 0.004 | 9 |
| Vasculitis | Chronic myeloid leukemia signalling | FGFR2, PIK3R3, PIK3C2A, RBL2, RAF1, TGFB2, PIK3R1, TP53, CTBP2, FRS2, SMAD3, GRB2, RBL1, CDK6, FGFR4, RB1 | 16 | 1.70 | 0.006 | 7 |
| Vasculitis | Synaptic long-term depression | IGF1R, GNAS, ITPR3, RAF1, PRKG1, GNA12, PRKG2, ITPR1, PRKCZ | 9 | 1.66 | 0.006 | 192 |
| Cancer overall | Adipogenesis pathway | FGFR2, NFATC4, WNT5A, BMP2, CLOCK, TP53, KLF3, EZH2, ARNTL, CTBP2, SMAD3, SOX9, FGFR4 | 13 | 1.34 | < 0.001 | 85 |
| Cancer overall | Molecular mechanisms of cancer | FGFR2, LRP5, PIK3C2A, PTCH1, WNT5A, RHOD, ARHGEF12, GNA12, SMAD6, BMP2, PIK3R1, MAX, NFKBIA, TP53, CCND3, SMAD7, FRS2, SMAD3, GRB2, BMP6, CREBBP, RBL1, CDK6, FGFR4, PRKCZ, PIK3R3, IHH, CTNNB1, RAF1, TGFB2, GNAS, MAP2K4, TAB1, WNT4, RB1, ADCY9 | 36 | 1.14 | 0.002 | 1 |
| Cancer overall | CTLA4 signalling in cytotoxic T lymphocytes | FGFR2, PIK3R3, PIK3C2A, FRS2, GRB2, HLA-C, PIK3R1, FGFR4, ZAP70 | 9 | 1.25 | 0.006 | 148 |
| Cancer overall | Systemic lupus erythematosus signalling | FGFR2, NFATC4, MTOR, PIK3R3, PIK3C2A, SNRPE, PIK3R1, NFATC1, NFATC3, FRS2, GRB2, HLA-C, FGFR4 | 13 | 1.21 | 0.006 | 182 |
| Cancer overall | Sphingosine-1-phosphate signalling | S1PR2, FGFR2, PIK3R3, PIK3C2A, FRS2, RHOD, GNA12, GRB2, PIK3R1, FGFR4, ADCY9 | 11 | 1.20 | 0.008 | 122 |
| Breast cancer | Hypoxia signalling in the cardiovascular system | CREB5, UBE2Z, CREBBP, NFKBIA, TP53 | 5 | 0.36 | < 0.001 | 202 |
| Breast cancer | PCP pathway | WNT5A, MAP2K4, ROR2, WNT4, DAAM1 | 5 | 2.06 | 0.038 | 198 |
| Colorectal cancer | SAPK/JNK signalling | FGFR2, PIK3R3, PIK3C2A, GNA12, PIK3R1, NFATC1, TP53, NFATC3, MAP2K4, FRS2, GRB2, TAB1, FGFR4, MAP3K3 | 14 | 2.32 | < 0.001 | 20 |
| Colorectal cancer | Signalling by rho family GTPases | FGFR2, PIK3R3, PIK3C2A, SLC9A1, RHOD, RAF1, ARHGEF12, GNA12, PIK3R1, GNAS, MAP2K4, FRS2, GRB2, CDC42EP3, FGFR4, PRKCZ | 16 | 2.27 | < 0.001 | 141 |
| Colorectal cancer | Small cell lung cancer signalling | FGFR2, PIK3R3, PIK3C2A, PIK3R1, MAX, NFKBIA, TP53, FRS2, GRB2, RXRA, CDK6, FGFR4, RB1 | 13 | 2.45 | < 0.001 | 17 |
| Colorectal cancer | Sphingosine-1-phosphate signalling | S1PR2, FGFR2, PIK3R3, PIK3C2A, FRS2, RHOD, GNA12, GRB2, PIK3R1, FGFR4, ADCY9 | 11 | 2.47 | < 0.001 | 122 |
| Colorectal cancer | Xenobiotic metabolism signalling | FGFR2, PIK3R3, NCOA1, SMOX, PIK3C2A, RAF1, PIK3R1, MAP2K4, FRS2, GRB2, RXRA, CREBBP, FGFR4, PRKCZ, MAP3K3 | 15 | 2.16 | < 0.001 | 185 |
# Rank indicates the rank of the height pathway as shown in Additional file 1: Table S6; Odds ratio and p value indicate the association of the height and the risks of diseases through the pathways
Abbreviations: cAMP cyclic adenosine monophosphate, CLTA4 cytotoxic T-lymphocyte-associated protein 4, DARPP32 dopamine- and cAMP-regulated phosphoprotein Mr 32 kDa, eNOS endothelial nitric oxide synthesis, ERK5 extracellular signal regulated kinase 5, GPCR G protein-coupled receptor, GTP guanosine-5′-triphosphate, HER-2 human epidermal growth factor 2, JNK Jun amino terminal kinase, IL interlukin, mTOR mammalian target of rapamycin, NFAT nuclear factor of activated T cells, NGF nerve growth factor, NRF2 nuclear factor erythroid 2–related factor 2, Oct4 octamer-binding transcription factor 4, PCP planar cell polarity, PI3K phosphoinositide-3-kinase, RAR retinoic acid receptor, RXR retinoid X receptor, SAPK stress-activated protein kinase, TGF-β transforming growth factor beta, Wnt wingless-related integration site, VDR vitamin D receptor