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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