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Table 4 Top pathways showing the association of height with diseases

From: Adult height and risk of 50 diseases: a combined epidemiological and genetic analysis

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
  1. # 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
  2. 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