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. 2020 Jul 29;268(1):114–124. doi: 10.1007/s00415-020-10119-8

Table 2.

Associations between exposures and multiple sclerosis in Mendelian randomization analyses

IVW-random effects method Weighted median method MR-PRESSO Cochrane’s Q Phet Pintercept
Exposure OR 95% CI p OR 95% CI p OR 95% CI p
Psychiatric factor
 Lifetime anxiety disorder 0.95 0.76–1.18 0.617 1.03 0.86–1.25 0.720 1.02 0.85–1.22 0.840 13.0 0.011 0.673
 Major depressive disorder 1.03 0.79–1.35 0.812 0.99 0.75–1.31 0.948 1.04 0.83–1.29 0.753 220.2  < 0.001 0.723
 Sleep duration in hour 1.00 0.99–1.01 0.970 1.00 0.99–1.01 0.523 1.00 0.99–1.01 0.846 138.4  < 0.001 0.378
 Short sleep (< 7 h) 1.31 0.99–1.74 0.055 1.06 0.76–1.48 0.741 1.31 0.99–1.74 0.068 39.7 0.023 0.621
 Long sleep (> 9 h) 1.09 0.72–1.65 0.677 1.15 0.81–1.63 0.429 1.03 0.78–1.36 0.848 12.7 0.026 0.237
 Insomnia 1.00 0.88–1.13 0.950 1.06 0.97–1.15 0.235 1.07 1.00–1.15 0.050 1014.8  < 0.001 0.809
 Morningness 0.98 0.85–1.13 0.780 0.92 0.82–1.02 0.111 0.95 0.87–1.03 0.189 1282.4  < 0.001 0.134
 Restless leg syndrome 0.98 0.93–1.04 0.535 1.00 0.92–1.08 0.985 0.98 0.93–1.04 0.542 20.2 0.384 0.561
Autoimmune disorder
 Type 1 diabetes 1.09 0.93–1.29 0.288 1.00 0.91–1.09 0.963 1.05 0.99–1.13 0.162 192.2  < 0.001 0.318
 Latent autoimmune diabetes in adults 0.99 0.59–1.64 0.962 1.07 0.97–1.17 0.173 – – – 89.5  < 0.001 0.268
 Allergic rhinitis 0.85 0.59–1.22 0.365 1.00 0.82–1.21 0.972 0.88 0.77–1.02 0.100 324.5  < 0.001 0.361
 Asthma 0.96 0.82–1.12 0.598 0.97 0.87–1.08 0.554 0.94 0.86–1.03 0.190 88.8  < 0.001 0.089
 Eczema (atopic dermatitis) 1.33 0.81–2.18 0.256 1.06 0.88–1.28 0.532 1.31 1.09–1.57 0.018 489.4  < 0.001 0.497
 Rheumatoid arthritis 1.05 0.87–1.27 0.598 0.95 0.82–1.09 0.437 1.02 0.90–1.15 0.801 147.2  < 0.001 0.050
Cardiometabolic factor
 Type 2 diabetes 1.08 0.99–1.19 0.089 1.11 1.01–1.21 0.029 1.10 1.04–1.16 5.7 × 10–4 737.9  < 0.001 0.978
 Fasting glucose 1.14 0.90–1.46 0.282 1.01 0.80–1.27 0.956 1.14 0.85–1.53 0.405 93.0  < 0.001 0.72
 Fasting insulin 1.08 0.72–1.61 0.721 1.12 0.72–1.72 0.620 0.90 0.26–3.09 0.743 31.4 0.018 0.268
 Hemoglobin A1c 0.86 0.51–1.47 0.590 0.92 0.56–1.53 0.761 1.15 0.76–1.74 0.518 109.7  < 0.001 0.973
 Hemoglobin 1.24 0.83–1.84 0.294 1.41 1.02–1.94 0.038 1.41 1.02–1.93 0.061 75.3  < 0.001 0.749
 Diastolic blood pressure 1.00 0.98–1.02 0.978 1.00 0.97–1.02 0.906 1.00 0.98–1.02 0.698 476.6  < 0.001 0.519
 Systolic blood pressure 1.00 0.98–1.01 0.681 0.99 0.98–1.01 0.386 1.00 0.98–1.01 0.445 340.1  < 0.001 0.475
 Coronary artery disease 0.99 0.90–1.09 0.917 1.00 0.92–1.09 0.976 0.97 0.90–1.04 0.358 140.1  < 0.001 0.822
 Peripheral artery disease 1.17 0.92–1.49 0.214 1.16 0.93–1.43 0.183 1.08 0.91–1.29 0.387 51.1  < 0.001 0.745
Obesity-related factor
 Birthweight 0.94 0.68–1.30 0.700 0.97 0.76–1.23 0.787 0.97 0.79–1.20 0.773 433.0  < 0.001 0.718
 Childhood body mass index 1.23 1.05–1.43 0.010 1.20 0.97–1.48 0.089 1.22 1.07–1.40 0.011 9.4 0.743 0.862
 Adulthood body mass index 1.27 1.1.5–1.41 2 × 10–6 1.25 1.08–1.44 0.003 1.28 1.16–1.40 2.9 × 10–7 1500.9  < 0.001 0.452
 Waist circumference 1.20 0.97–1.48 0.096 1.27 1.06–1.53 0.010 1.30 1.14–1.47 7.0 × 10–5 1239.9  < 0.001 0.753
 Lean body mass 1.06 0.95–1.18 0.311 1.02 0.90–1.15 0.756 1.05 0.94–1.17 0.464 14.7 0.023 0.843
 Body fat percentage 1.18 0.97–1.43 0.089 1.27 1.08–1.50 0.004 1.26 1.12–1.43 2.1 × 10–4 1345.1  < 0.001 0.909
 Circulating adiponectin 1.00 0.83–1.20 0.982 1.03 0.81–1.31 0.807 1.00 0.83–1.20 0.982 9.8 0.369 0.970
Hormone-related factor
 Age of puberty 0.90 0.80–1.01 0.073 0.97 0.88–1.08 0.613 0.90 0.85–0.97 0.004 1224.3  < 0.001 0.128
 Age of natural menopause 0.98 0.93–1.03 0.395 1.00 0.96–1.05 0.943 0.99 0.96–1.03 0.771 126.7  < 0.001 0.464
Other factors
 Migraine 1.09 0.93–1.28 0.267 1.10 0.92–1.31 0.283 1.08 0.93–1.24 0.317 64.2  < 0.001 0.838
 Migraine without aura 1.03 0.93–1.14 0.574 1.02 0.91–1.14 0.789 0.180
 Estimated bone mineral density 1.02 0.95–1.10 0.569 1.11 0.98–1.25 0.089 1.05 0.98–1.12 0.164 1340.7  < 0.001 0.633
 Uric acid 1.03 0.92–1.14 0.633 1.00 0.92–1.09 0.952 1.01 0.93–1.10 0.743 265.7  < 0.001 0.621
Amino acid
 Carnitine 0.99 0.90–1.09 0.898 1.07 0.98–1.16 0.120 1.03 0.98–1.08 0.313 42.2  < 0.001 0.206
 Homocysteine 0.87 0.68–1.12 0.289 0.87 0.69–1.09 0.227 0.93 0.80–1.08 0.374 24.7 0.010 0.614
 Isoleucine 0.98 0.69–1.38 0.892 1.03 0.76–1.39 0.844 0.98 0.69–1.38 0.892 7.8 0.050 0.579
Plasma fatty acid
 Docosapentaenoic acid 1.03 0.71–1.50 0.867 1.05 0.72–1.53 0.805 – – – 1.2 0.544 0.476
 Linoleic acid 0.99 0.98–1.02 0.762 0.99 0.97–1.02 0.552 – – – 2.9 0.235 0.527
 Palmitoleic acid 0.96 0.82–1.11 0.571 0.92 0.77–1.10 0.352 0.96 0.82–1.11 0.571 4.9 0.296 0.472
 Stearic acid 1.09 0.96–1.21 0.194 1.06 0.93–1.20 0.418 – – – 1.3 0.522 0.584
Mineral
 Calcium 0.78 0.33–1.83 0.564 0.88 0.50–1.54 0.644 0.98 0.54–1.77 0.940 18.9 0.004 0.741
 Magnesium 1.16 0.94–1.44 0.172 1.19 0.91–1.54 0.199 1.16 0.94–1.44 0.172 1.7 0.789 0.412
 Sodium 2.16 1.00–4.68 0.050 1.41 0.56–3.55 0.461 2.16 1.00–4.68 0.050 78.9  < 0.001 0.642
 Potassium 0.74 0.13–4.23 0.736 1.39 0.24–8.04 0.713 1.16 0.30–4.50 0.836 22.5 0.021 0.113
 Iron 1.10 0.81–1.50 0.158 0.92 0.77–1.11 0.395 1.04 0.73–1.48 0.846 31.8  < 0.001 0.949
Vitamin
 Folate (vitamin B9) 1.48 0.86–2.54 0.153 1.47 1.01–2.16 0.047 – – – 4.4 0.037 0.576
 Vitamin B12 0.91 0.72–1.16 0.446 0.90 0.73–1.11 0.337 0.94 0.72–1.23 0.668 28.4  < 0.001 0.183
 Vitamin D 0.77 0.65–0.93 0.005 0.83 0.72–0.95 0.006 0.85 0.78–0.94 0.029 17.3 0.004 0.981
 Vitamin E 0.75 0.34–1.66 0.481 0.89 0.33–2.38 0.814 – – – 2.4 0.293 0.988
Lifestyle factor
 Alcohol drinking 0.73 0.47–1.12 0.149 1.13 0.64–1.99 0.675 0.78 0.53–1.16 0.224 140.0  < 0.001 0.407
 Coffee intake 1.00 0.99–1.01 0.969 1.01 0.99–1.02 0.099 1.00 0.99–1.01 0.538 20.0 0.045 0.597
 Smoking initiation 1.04 0.91–1.19 0.550 1.12 0.96–1.32 0.146 1.05 0.93–1.19 0.420 469.2  < 0.001 0.774
 Physical activity 0.12 0.05–0.32 2 × 10–5 0.24 0.07–0.90 0.039 0.15 0.06–0.40 0.012 12.0 0.062 0.066
Serum lipids
 High-density lipoprotein cholesterol 1.14 1.00–1.31 0.057 1.07 0.93–1.22 0.345 1.17 1.06–1.29 0.004 172.0  < 0.001 0.707
 Low-density lipoprotein cholesterol 0.95 0.75–1.19 0.651 1.12 0.96–1.31 0.155 0.96 0.86–1.07 0.499 411.6  < 00.01 0.222
 Total cholesterol 0.98 0.79–1.23 0.887 1.16 0.99–1.35 0.068 1.00 0.88–1.13 0.951 501.2  < 0.001 0.858
 Triglycerides 0.90 0.79–1.02 0.098 0.94 0.81–1.09 0.385 0.88 0.78–1.00 0.052 60.0 0.007 0.808
Inflammatory biomarker
 Tumor necrosis factor 8.83 0.33–237 0.194 5.80 2.06–16.3 0.001 – – – 60.7  < 0.001 0.082
 C-reactive protein 1.08 0.85–1.38 0.538 0.99 0.84–1.17 0.940 1.08 0.94–1.24 0.262 386.4  < 0.001 0.681
 Immunoglobulin E 0.89 0.76–1.05 0.162 0.93 0.78–1.10 0.389 – – – 1.6 0.443 0.825
Socioeconomic status
 Education level 0.91 0.78–1.06 0.236 0.93 0.77–1.12 0.430 0.90 0.79–1.02 0.108 1367.8  < 0.001 0.284
 Intelligence 1.08 0.91–1.29 0.369 1.04 0.85–1.28 0.707 1.08 0.93–1.25 0.294 365.8  < 0.001 0.392

CI indicates confidence interval; IVW, inverse weighted median; OR, odd ratio. P for pleiotropy is the p value for the intercept of MR-Egger analysis (p < 0.05 indicates the possible pleiotropy)