Background
Methods
Study design and setting
Study participants
Disease definition
Statistical analysis
Epidemiological analysis
Genetic analysis
Sensitivity analysis
Genetic score for height
Pathway analysis
Results
Characteristic | Height (cm) | Overall | |||
---|---|---|---|---|---|
Quartile 1 | Quartile 2 | Quartile 3 | Quartile 4 | ||
Height (cm)—female | 132–< 158 | 158–< 163 | 163–< 167 | 167–199 | 132–199 |
Height (cm)—male | 132–< 171 | 171–< 176 | 176–< 180 | 180–205 | 132–205 |
N | 87,358 | 117,771 | 97,416 | 114,889 | 417,434 |
Age | 58.8 (7.5) | 57.5 (7.8) | 56.4 (7.9) | 54.9 (8.1) | 56.8 (8.0) |
Sex—female | 52.8% | 55.7% | 55.7% | 51.6% | 54.0% |
Body mass index (BMI) | 28.1 (4.9) | 27.6 (4.8) | 27.2 (4.7) | 26.8 (4.6) | 27.4 (4.8) |
Obese (BMI ≥ 30) | 28.9% | 25.4% | 23.0% | 20.4% | 24.2% |
Waist-hip-ratio (WHR) | 0.88 (0.1) | 0.87 (0.1) | 0.87 (0.1) | 0.87 (0.1) | 0.87 (0.1) |
Townsend deprivation indexa | 22.5% | 18.1% | 16.7% | 16.1% | 18.1% |
Ever smoker | 47.1% | 46.2% | 45.5% | 45.5% | 46.0% |
Vigorous activityb | 55.5% | 58.8% | 60.6% | 63.0% | 59.7% |
Systolic BP (mmHg) | 145.3 (21.3) | 142.3 (20.8) | 140.1 (20.5) | 137.8 (19.5) | 141.2 (20.7) |
Diastolic BP (mmHg) | 85.4 (11.3) | 84.6 (11.3) | 84.0 (11.3) | 83.4 (11.2) | 84.3 (11.3) |
Female only | |||||
Nulliparous | 15.9% | 17.3% | 19.0% | 22.7% | 18.8% |
Ever oral contraceptive | 78.1% | 81.3% | 83.3% | 84.9% | 82.0% |
Ever on hormone replacement therapy | 45.0% | 41.6% | 38.1% | 33.4% | 39.3% |
Characteristic | Weighted genetic score for heighta | |||
---|---|---|---|---|
Quartile 1 | Quartile 2 | Quartile 3 | Quartile 4 | |
N | 90,170 | 107,870 | 109,390 | 110,004 |
Height (cm)—female | 159.2 (5.7) | 161.6 (5.6) | 163.3 (5.7) | 165.8 (6.0) |
Height (cm)—male | 172.1 (6.2) | 174.7 (6.2) | 176.6 (6.2) | 179.3 (6.5) |
Age | 56.7 (8.0) | 56.8 (8.0) | 56.8 (8.0) | 56.9 (7.9) |
Sex—female | 53.9% | 54.0% | 53.8% | 54.2% |
Body mass index (BMI) | 27.6 (4.9) | 27.5 (4.8) | 27.3 (4.7) | 27.2 (4.7) |
Obese (BMI ≥ 30) | 25.5% | 24.5% | 23.8% | 23.1% |
Waist-hip-ratio (WHR) | 0.87 (0.09) | 0.87 (0.09) | 0.87 (0.09) | 0.87 (0.09) |
Townsend deprivation indexb | 19.5% | 18.2% | 17.8% | 17.4% |
Ever smoker | 46.2% | 46.2% | 45.8% | 45.9% |
Vigorous activityc | 59.4% | 59.7% | 60.1% | 59.4% |
Systolic BP (mmHg) | 141.7 (20.9) | 141.4 (20.7) | 141.0 (20.6) | 140.6 (20.5) |
Diastolic BP (mmHg) | 84.6 (11.3) | 84.4 (11.3) | 84.2 (11.2) | 84.1 (11.3) |
Female only | ||||
Nulliparous | 18.7% | 18.4% | 18.7% | 19.5% |
Ever contraceptive pill | 81.9% | 82.0% | 82.2% | 82.0% |
Ever on hormone replacement therapy | 38.8% | 39.2% | 39.4% | 39.8% |
Association of height with diseases based on epidemiological and genetic analyses
Sensitivity analysis
Disease | Inverse-variance-based method | p value intercept (MR-Egger) | MR-Egger | p value intercept (robust MR-Egger) | Robust MR-Egger | Simple median | Weighted median | Penalised weighted median |
---|---|---|---|---|---|---|---|---|
CAD | 0.86 (0.82–0.90) | 0.163 | 0.93 (0.84–1.03) | 0.500 | 0.89 (0.80–1.00) | 0.87 (0.83–0.92) | 0.88 (0.83–0.93) | 0.88 (0.83–0.93) |
Hypertension | 0.88 (0.85–0.91) | 0.224 | 0.92 (0.86–0.99) | 0.138 | 0.96 (0.88–1.04) | 0.90 (0.88–0.93) | 0.91 (0.88–0.93) | 0.91 (0.88–0.93) |
AF | 1.33 (1.26–1.40) | 0.444 | 1.39 (1.24–1.56) | 0.436 | 1.40 (1.23–1.60) | 1.36 (1.28–1.44) | 1.34 (1.26–1.42) | 1.34 (1.26–1.43) |
VTE | 1.15 (1.11–1.19) | 0.147 | 1.23 (1.11–1.36) | 0.434 | 1.18 (1.06–1.32) | 1.14 (1.08–1.21) | 1.18 (1.11–1.24) | 1.16 (1.10–1.23) |
GORD | 0.94 (0.92–0.97) | 0.595 | 0.93 (0.87–1.00) | 0.695 | 0.94 (0.86–1.02) | 0.96 (0.92–1.00) | 0.95 (0.91–0.99) | 0.96 (0.92–0.99) |
Diaphragmatic hernia | 0.91 (0.88–0.94) | 0.516 | 0.88 (0.81–0.96) | 0.813 | 0.91 (0.83–1.00) | 0.94 (0.90–0.98) | 0.93 (0.89–0.97) | 0.93 (0.89–0.97) |
IDD | 1.14 (1.09–1.20) | 0.041 | 1.29 (1.15–1.45) | 0.198 | 1.22 (1.08–1.38) | 1.14 (1.07–1.20) | 1.13 (1.06–1.20) | 1.12 (1.05–1.19) |
Hip fracture | 1.27 (1.17–1.39) | 0.104 | 1.52 (1.20–1.92) | 0.134 | 1.48 (1.17–1.87) | 1.24 (1.08–1.42) | 1.23 (1.07–1.42) | 1.23 (1.07–1.41) |
Vasculitis | 1.20 (1.14–1.28) | 0.139 | 1.33 (1.15–1.54) | 0.240 | 1.32 (1.11–1.57) | 1.21 (1.10–1.32) | 1.22 (1.12–1.34) | 1.22 (1.11–1.33) |
Cancer overall | 1.06 (1.04–1.08) | 0.514 | 1.04 (0.99–1.10) | 0.536 | 1.04 (0.99–1.09) | 1.05 (1.02–1.09) | 1.05 (1.02–1.08) | 1.05 (1.02–1.08) |
Colorectal cancer | 1.11 (1.05–1.18) | 0.234 | 1.02 (0.86–1.20) | 0.173 | 0.99 (0.85–1.16) | 1.10 (1.00–1.21) | 1.06 (0.96–1.16) | 1.04 (0.95–1.15) |
Breast cancer | 1.07 (1.03–1.11) | 0.573 | 1.10 (0.98–1.23) | 0.930 | 1.06 (0.94–1.19) | 1.03 (0.97–1.10) | 1.04 (0.98–1.11) | 1.02 (0.96–1.09) |
Genetic score of height and odds ratios of diseases
Biological pathways
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 |