Table 1.
MR estimates from the four main analyses
| Exposure | Outcome | IVW | MR-Egger | MBE | WMM | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| β (se) | FDR-Q value | Cochran's Q value | FDR-Q value | Slope (se) | FDR-Q value | Intercept (se) | FDR-Q value | Cochran's Q value | FDR-Q value | β (se) | FDR-Q value | β (se) | FDR-Q value | ||
| ALT | Hepatitis NOS | 0.221 (0.036) | 1.75E-08 | 75.9 | 1.70E-01 | 0.246 (0.066) | 5.01E-04 | − 0.013 (0.027) | 6.97E-01 | 75.6 | 1.64E-01 | 0.261 (0.053) | 4.11E-06 | 0.286 (0.050) | 1.33E-07 |
| Malignant neoplasm of liver, primary | 0.275 (0.052) | 1.01E-06 | 67.2 | 2.57E-01 | 0.358 (0.094) | 4.36E-04 | − 0.043 (0.040) | 3.69E-01 | 65.9 | 2.75E-01 | 0.332 (0.087) | 4.36E-04 | 0.309 (0.084) | 6.56E-04 | |
| Type 2 diabetes | 0.023 (0.006) | 4.36E-04 | 50.0 | 3.67E-01 | 0.004 (0.011) | 7.46E-01 | 0.009 (0.004) | 6.33E-02 | 45.2 | 4.95E-01 | 0.025 (0.009) | 9.26E-03 | 0.023 (0.009) | 1.49E-02 | |
| Disorders of iron metabolism | 0.112 (0.025) | 3.07E-05 | 44.2 | 9.42E-01 | 0.139 (0.046) | 4.94E-03 | − 0.013 (0.019) | 5.70E-01 | 43.7 | 9.33E-01 | 0.140 (0.045) | 4.57E-03 | 0.118 (0.042) | 9.26E-03 | |
| Dementias | − 0.029 (0.021) | 2.25E-01 | 46.3 | 9.06E-01 | 0.011 (0.039) | 8.01E-01 | − 0.019 (0.016) | 2.94E-01 | 44.8 | 9.26E-01 | − 0.022 (0.039) | 6.38E-01 | − 0.014 (0.035) | 7.45E-01 | |
| Alcoholic liver damage | 0.157 (0.028) | 1.67E-07 | 66.6 | 2.48E-01 | 0.124 (0.056) | 4.45E-02 | 0.014 (0.021) | 5.89E-01 | 66.1 | 2.37E-01 | 0.149 (0.056) | 1.39E-02 | 0.150 (0.039) | 3.94E-04 | |
| Corneal degenerations | − 0.240 (0.056) | 7.68E-05 | 41.4 | 9.42E-01 | − 0.306 (0.107) | 8.57E-03 | 0.030 (0.042) | 5.69E-01 | 40.9 | 9.42E-01 | − 0.280 (0.103) | 1.20E-02 | − 0.287 (0.084) | 1.47E-03 | |
| Esophageal bleeding | 0.077 (0.016) | 8.11E-06 | 62.7 | 3.89E-01 | 0.111 (0.029) | 4.85E-04 | − 0.017 (0.012) | 2.37E-01 | 60.7 | 4.43E-01 | 0.124 (0.026) | 1.28E-05 | 0.116 (0.024) | 6.13E-06 | |
| Other chronic non-alcoholic liver disease | 0.186 (0.019) | 5.13E-20 | 69.1 | 2.01E-01 | 0.209 (0.039) | 5.82E-07 | − 0.010 (0.015) | 5.82E-01 | 68.5 | 1.98E-01 | 0.114 (0.053) | 5.29E-02 | 0.181 (0.027) | 1.22E-09 | |
| Cirrhosis of liver without mention of alcohol | 0.211 (0.032) | 1.22E-09 | 35.6 | 9.42E-01 | 0.251 (0.064) | 2.88E-04 | − 0.016 (0.023) | 5.69E-01 | 35.3 | 9.33E-01 | 0.285 (0.069) | 1.40E-04 | 0.264 (0.047) | 1.98E-07 | |
| Liver abscess and sequelae of chronic liver disease | 0.110 (0.031) | 1.00E-03 | 65.3 | 2.38E-01 | 0.122 (0.057) | 5.19E-02 | − 0.006 (0.024) | 8.09E-01 | 65.1 | 2.08E-01 | 0.150 (0.047) | 2.99E-03 | 0.154 (0.045) | 1.47E-03 | |
| Portal hypertension | 0.206 (0.034) | 2.42E-08 | 61.1 | 2.38E-01 | 0.244 (0.067) | 6.74E-04 | − 0.016 (0.025) | 5.89E-01 | 61.0 | 2.07E-01 | 0.224 (0.074) | 4.94E-03 | 0.220 (0.051) | 6.44E-05 | |
| Hepatomegaly | 0.145 (0.038) | 3.55E-04 | 54.8 | 6.74E-01 | 0.097 (0.069) | 2.22E-01 | 0.024 (0.029) | 4.92E-01 | 54.1 | 6.62E-01 | 0.121 (0.106) | 3.27E-01 | 0.148 (0.066) | 4.41E-02 | |
| Abnormal results of function study of liver | 0.071 (0.012) | 1.48E-07 | 63.0 | 2.48E-01 | 0.035 (0.022) | 1.60E-01 | 0.017 (0.009) | 7.78E-02 | 58.7 | 3.31E-01 | 0.050 (0.018) | 1.20E-02 | 0.048 (0.018) | 1.34E-02 | |
| Cholelithiasis | 0.041 (0.010) | 1.83E-04 | 77.5 | 9.09E-02 | 0.029 (0.021) | 2.25E-01 | 0.005 (0.008) | 5.95E-01 | 76.8 | 8.06E-02 | 0.047 (0.018) | 1.80E-02 | 0.042 (0.013) | 2.93E-03 | |
| Fracture of hand or wrist | − 0.049 (0.012) | 1.42E-04 | 41.2 | 9.42E-01 | − 0.067 (0.023) | 6.14E-03 | 0.008 (0.009) | 4.43E-01 | 40.4 | 9.42E-01 | − 0.044 (0.022) | 6.67E-02 | − 0.041 (0.020) | 6.05E-02 | |
| AST | Cancer of gums | − 0.788 (0.132) | 1.18E-07 | 87.2 | 4.97E-01 | − 0.604 (0.244) | 3.91E-02 | − 0.066 (0.073) | 4.87E-01 | 86.3 | 4.95E-01 | − 1.052 (1.535) | 6.15E-01 | − 1.034 (0.222) | 5.58E-05 |
| Thyrotoxicosis with or without goiter | − 0.087 (0.028) | 8.47E-03 | 76.2 | 2.57E-01 | − 0.090 (0.055) | 1.95E-01 | 0.001 (0.014) | 9.54E-01 | 76.1 | 2.37E-01 | − 0.092 (0.051) | 1.52E-01 | − 0.068 (0.041) | 1.83E-01 | |
| Graves' disease | 0.058 (0.046) | 3.21E-01 | 68.4 | 4.83E-01 | 0.143 (0.082) | 1.63E-01 | − 0.029 (0.023) | 3.21E-01 | 65.4 | 5.35E-01 | 0.099 (0.063) | 2.10E-01 | 0.075 (0.065) | 3.56E-01 | |
| Hypothyroidism NOS | − 0.027 (0.009) | 1.03E-02 | 59.8 | 5.15E-01 | − 0.033 (0.017) | 1.10E-01 | 0.002 (0.004) | 7.70E-01 | 59.5 | 4.95E-01 | − 0.029 (0.015) | 1.08E-01 | − 0.021 (0.014) | 2.08E-01 | |
| Type 1 diabetes | − 0.006 (0.111) | 9.58E-01 | 60.5 | 8.58E-01 | − 0.051 (0.215) | 8.65E-01 | 0.013 (0.056) | 8.65E-01 | 60.5 | 8.25E-01 | − 0.018 (0.341) | 9.59E-01 | − 0.043 (0.174) | 8.65E-01 | |
| Disorders of iron metabolism | 0.104 (0.041) | 3.62E-02 | 90.5 | 1.70E-01 | 0.091 (0.081) | 3.77E-01 | 0.004 (0.021) | 8.98E-01 | 90.4 | 1.64E-01 | 0.146 (0.082) | 1.54E-01 | 0.151 (0.061) | 3.96E-02 | |
| Multiple sclerosis | − 0.081 (0.024) | 3.48E-03 | 90.0 | 2.48E-01 | − 0.102 (0.042) | 4.23E-02 | 0.008 (0.013) | 6.64E-01 | 89.8 | 2.37E-01 | − 0.052 (0.034) | 2.21E-01 | − 0.046 (0.034) | 2.77E-01 | |
| Varicose veins of lower extremity | 0.039 (0.009) | 3.17E-04 | 85.9 | 2.10E-01 | 0.023 (0.016) | 2.45E-01 | 0.006 (0.005) | 3.26E-01 | 84.8 | 2.07E-01 | 0.038 (0.013) | 1.40E-02 | 0.035 (0.014) | 3.62E-02 | |
| Epistaxis or throat hemorrhage | 0.089 (0.020) | 1.54E-04 | 115.7 | 2.90E-02 | 0.062 (0.037) | 1.90E-01 | 0.010 (0.011) | 4.87E-01 | 115.0 | 2.59E-02 | 0.075 (0.027) | 2.24E-02 | 0.052 (0.027) | 1.23E-01 | |
| Hereditary disturbances in tooth structure | − 0.540 (0.134) | 4.46E-04 | 101.7 | 1.70E-01 | − 0.463 (0.242) | 1.19E-01 | − 0.028 (0.072) | 7.83E-01 | 101.7 | 1.64E-01 | − 0.390 (1.479) | 8.64E-01 | − 0.547 (0.215) | 3.62E-02 | |
| Celiac disease | − 0.399 (0.104) | 8.92E-04 | 28.1 | 1.36E-01 | − 0.365 (0.237) | 2.21E-01 | − 0.006 (0.036) | 9.01E-01 | 28.1 | 1.06E-01 | − 0.297 (0.138) | 7.83E-02 | − 0.345 (0.106) | 5.59E-03 | |
| Other chronic non-alcoholic liver disease | 0.125 (0.025) | 1.72E-05 | 89.9 | 2.48E-01 | 0.086 (0.057) | 2.37E-01 | 0.011 (0.014) | 5.83E-01 | 89.3 | 2.37E-01 | 0.158 (0.072) | 6.95E-02 | 0.113 (0.035) | 5.76E-03 | |
| Hematuria | 0.012 (0.008) | 2.43E-01 | 45.7 | 9.42E-01 | 0.020 (0.015) | 2.90E-01 | − 0.002 (0.004) | 6.60E-01 | 45.4 | 9.33E-01 | 0.019 (0.014) | 2.77E-01 | 0.017 (0.013) | 3.20E-01 | |
| Dermatitis herpetiformis | − 0.585 (0.162) | 1.98E-03 | 96.4 | 1.36E-01 | − 0.539 (0.332) | 1.96E-01 | − 0.014 (0.086) | 9.01E-01 | 96.4 | 1.08E-01 | − 0.564 (1.020) | 6.86E-01 | − 0.612 (0.226) | 2.56E-02 | |
| Ankylosing spondylitis | 0.104 (0.047) | 6.61E-02 | 102.9 | 8.07E-02 | 0.076 (0.081) | 4.67E-01 | 0.011 (0.025) | 7.70E-01 | 102.5 | 7.00E-02 | 0.075 (0.057) | 2.98E-01 | 0.113 (0.061) | 1.34E-01 | |
| Hallux valgus (Bunion) | 0.055 (0.012) | 3.88E-05 | 89.5 | 2.10E-01 | 0.044 (0.020) | 6.76E-02 | 0.004 (0.006) | 6.06E-01 | 88.9 | 2.01E-01 | 0.033 (0.016) | 7.91E-02 | 0.040 (0.016) | 3.91E-02 | |
| Other ill-defined and unknown causes of morbidity and mortality | 0.036 (0.007) | 2.72E-06 | 91.4 | 3.87E-01 | 0.045 (0.012) | 1.03E-03 | − 0.003 (0.004) | 4.67E-01 | 90.4 | 4.00E-01 | 0.034 (0.013) | 3.39E-02 | 0.028 (0.011) | 3.62E-02 | |
| GGT | Other chronic non-alcoholic liver disease | 0.026 (0.004) | 4.48E-09 | 146.0 | 1.70E-01 | 0.020 (0.007) | 9.02E-03 | 0.008 (0.008) | 4.09E-01 | 144.9 | 1.64E-01 | 0.022 (0.007) | 3.05E-03 | 0.021 (0.007) | 4.87E-03 |
| Abnormal results of function study of liver | 0.028 (0.003) | 6.00E-20 | 146.5 | 1.70E-01 | 0.019 (0.005) | 4.74E-04 | 0.012 (0.006) | 4.08E-02 | 141.1 | 2.01E-01 | 0.022 (0.005) | 9.79E-05 | 0.026 (0.005) | 8.63E-08 | |
| Cholelithiasis | 0.012 (0.002) | 4.96E-08 | 137.5 | 1.99E-01 | 0.011 (0.004) | 3.95E-03 | 0.001 (0.004) | 7.98E-01 | 137.4 | 1.91E-01 | 0.014 (0.003) | 3.33E-05 | 0.014 (0.003) | 1.24E-04 | |
| ALP | Hypercholesterolemia | − 0.003 (0.001) | 6.10E-04 | 248.0 | 1.30E-02 | − 0.003 (0.001) | 2.74E-02 | 0.000 (0.002) | 9.89E-01 | 247.9 | 1.12E-02 | − 0.003 (0.001) | 4.38E-02 | − 0.004 (0.001) | 1.21E-02 |
| Pulmonary heart disease | − 0.013 (0.002) | 1.64E-07 | 244.4 | 6.56E-02 | − 0.013 (0.004) | 2.51E-03 | 0.000 (0.005) | 9.93E-01 | 244.4 | 5.78E-02 | − 0.007 (0.004) | 2.15E-01 | − 0.012 (0.003) | 2.51E-03 | |
| Phlebitis and thrombophlebitis of lower extremities | − 0.009 (0.002) | 2.51E-03 | 260.5 | 1.30E-02 | − 0.007 (0.004) | 2.15E-01 | − 0.003 (0.005) | 7.19E-01 | 260.3 | 1.12E-02 | − 0.008 (0.004) | 1.84E-01 | − 0.009 (0.004) | 3.67E-02 | |
| Circulatory disease NEC | − 0.001 (0.001) | 5.79E-01 | 273.7 | 5.64E-03 | − 0.003 (0.002) | 2.66E-01 | 0.003 (0.002) | 4.47E-01 | 272.0 | 6.16E-03 | 0.002 (0.003) | 7.08E-01 | 0.000 (0.002) | 9.89E-01 | |
MR Mendelian randomization, IVW inverse-variance weighting, MBE mode-based estimate method, WMM weighted median method, FDR false discovery rate, ALT alanine aminotransferase, AST aspartate aminotransferase, ALP alkaline phosphatase, GGT λ-glutamyl transferase
The estimates were derived from MR analyses based on untransformed liver enzyme levels, and the outliers identified by MR-PRESSO method have been removed
The P value in bold denotes statistical significance