Table 1 Sensitivity analysis results for the metabolites identified in primary analysis
Exposome components | Sample size | Cases | N SNPs | MR-Egger | Weighted median | MR-PRESSO | |||
|---|---|---|---|---|---|---|---|---|---|
OR (95% CI) | P-value | OR (95% CI) | P-value | OR (95% CI) | P-value | ||||
Disease | |||||||||
Atrial fibrillation and flutter | 361194 | 6356 | 25 | 0.92 (0.82, 1.03) | 0.148 | 0.93 (0.87, 1.00) | 0.062 | 0.91 (0.49, 1.7) | 1.53 × 10−04 |
Coronary atherosclerosis | 361194 | 14334 | 26 | 0.64 (0.5, 0.82) | 3.69 × 10−04 | 0.73 (0.65, 0.83) | 7.61 × 10−07 | 0.77 (0.43, 1.35) | 1.07 × 10−05 |
Cardiac arrhythmias, COPD co-morbidities | 361194 | 8801 | 20 | 0.93 (0.79, 1.09) | 0.349 | 0.9 (0.81, 0.99) | 0.032 | 0.86 (0.47, 1.57) | 6.77 × 10−05 |
Ischemic heart disease | 361194 | 20857 | 30 | 0.53 (0.28, 1.03) | 0.061 | 0.70 (0.60, 0.80) | 8.07 × 10−07 | 0.66 (0.11, 3.99) | 0.006 |
Angina (self-reported) | 361141 | 11370 | 13 | 0.56 (0.37, 0.84) | 0.005 | 0.75 (0.64, 0.89) | 6.88 × 10−04 | 0.72 (0.24, 2.14) | 2.19 × 10−04 |
Angina (diagnosed) | 360420 | 11372 | 14 | 0.54 (0.36, 0.81) | 0.003 | 0.75 (0.63, 0.89) | 0.001 | 0.73 (0.27, 2) | 1.58 × 10−04 |
Hypertension (self-reported) | 361141 | 93560 | 166 | 0.77 (0.58, 1.03) | 0.076 | 0.69 (0.61, 0.78) | 4.23 × 10−09 | 0.68 (0.64, 0.72) | 3.30 × 10−14 |
Hypertension (diagnosed) | 360420 | 97139 | 175 | 0.74 (0.56, 0.98) | 0.037 | 0.7 (0.62, 0.78) | 1.93 × 10−09 | 0.7 (0.66, 0.75) | 2.41 × 10−12 |
Diseases of the circulatory system | 361194 | 60504 | 9 | 0.24 (0.09, 0.65) | 0.005 | 0.42 (0.28, 0.63) | 3.48 × 10−05 | 0.43 (0.23, 0.8) | 5.52 × 10−04 |
High cholesterol (self-reported) | 361141 | 43957 | 58 | 0.73 (0.57, 0.93) | 0.010 | 0.83 (0.73, 0.94) | 0.005 | 0.81 (0.59, 1.1) | 5.80 × 10−04 |
Diabetes (self-reported) | 361141 | 14114 | 43 | 0.92 (0.78, 1.08) | 0.311 | 0.9 (0.82, 0.99) | 0.030 | 0.85 (0.56, 1.29) | 2.48 × 10−05 |
Diabetes (diagnosed) | 360192 | 17275 | 55 | 0.99 (0.85, 1.15) | 0.856 | 0.91 (0.83, 1) | 0.052 | 0.86 (0.62, 1.21) | 3.51 × 10−05 |
Malignant neoplasm of prostate | 361194 | 6321 | 24 | 0.99 (0.85, 1.15) | 0.891 | 0.88 (0.81, 0.95) | 6.72 × 10−04 | 0.91 (0.29, 2.84) | 0.004 |
Venous thromboembolism | 361194 | 4620 | 10 | 0.95 (0.87, 1.04) | 0.276 | 0.92 (0.87, 0.98) | 0.009 | 0.92 (0.16, 5.36) | 0.015 |
DVT of lower extremities | 361194 | 2116 | 7 | 0.96 (0.9, 1.02) | 0.201 | 0.95 (0.91, 0.99) | 0.024 | 0.94 (0.06, 15.71) | 0.022 |
DVT of lower extremities and pulmonary embolism | 361194 | 4319 | 11 | 0.95 (0.87, 1.04) | 0.239 | 0.93 (0.88, 0.99) | 0.017 | 0.92 (0.17, 4.99) | 0.011 |
No vascular/heart problems | 360420 | 253565 | 170 | 1.36 (1.01, 1.82) | 0.045 | 1.48 (1.31, 1.69) | 1.20 × 10−09 | 1.55 (1.47, 1.64) | 3.98 × 10−16 |
Physical measures | |||||||||
Systolic blood pressure | 340159 | - | 203 | 0.49 (0.25, 0.97) | 0.041 | 0.54 (0.41, 0.71) | 1.00 × 10−05 | 0.55 (0.44, 0.68) | 1.17 × 10−07 |
Diastolic blood pressure | 340162 | - | 178 | 0.77 (0.37, 1.59) | 0.478 | 0.55 (0.42, 0.72) | 1.38 × 10−05 | 0.56 (0.46, 0.69) | 1.20 × 10−07 |
Arm fat mass (right) | 354736 | - | 283 | 0.58 (0.39, 0.87) | 0.009 | 0.6 (0.48, 0.74) | 4.47 × 10−06 | 0.76 (0.66, 0.88) | 1.55 × 10−04 |
Arm fat percentage (left) | 354707 | - | 267 | 0.57 (0.3, 1.08) | 0.087 | 0.53 (0.39, 0.72) | 4.83 × 10−05 | 0.67 (0.54, 0.82) | 1.28 × 10−04 |
Arm fat percentage (right) | 354760 | - | 265 | 0.62 (0.32, 1.18) | 0.144 | 0.52 (0.38, 0.71) | 3.85 × 10−05 | 0.65 (0.53, 0.8) | 4.02 × 10−05 |
Leg fat mass (right) | 354807 | - | 287 | 0.46 (0.28, 0.78) | 0.004 | 0.58 (0.44, 0.77) | 1.55 × 10−04 | 0.67 (0.57, 0.8) | 5.95 × 10−06 |
Leg fat mass (left) | 354788 | - | 287 | 0.4 (0.24, 0.69) | 0.001 | 0.54 (0.41, 0.72) | 2.60 × 10−05 | 0.66 (0.55, 0.78) | 4.06 × 10−06 |
Leg fat percentage (right) | 354811 | - | 267 | 0.44 (0.13, 1.53) | 0.196 | 0.42 (0.29, 0.61) | 7.54 × 10−06 | 0.58 (0.42, 0.82) | 0.002 |
Leg fat percentage (left) | 354791 | - | 270 | 0.4 (0.12, 1.36) | 0.142 | 0.4 (0.28, 0.58) | 1.46 × 10−06 | 0.61 (0.44, 0.85) | 0.003 |
Trunk fat mass | 354597 | - | 298 | 0.67 (0.44, 1.03) | 0.068 | 0.68 (0.55, 0.83) | 1.91 × 10−04 | 0.77 (0.67, 0.89) | 2.71 × 10−04 |
Whole body fat mass | 354244 | - | 300 | 0.55 (0.37, 0.84) | 0.006 | 0.61 (0.49, 0.76) | 9.41 × 10−06 | 0.71 (0.62, 0.81) | 1.19 × 10−06 |
Waist circumference | 360564 | - | 252 | 0.73 (0.41, 1.32) | 0.302 | 0.62 (0.46, 0.82) | 7.92 × 10−04 | 0.73 (0.61, 0.88) | 0.001 |
Body mass index: by impedance measurement | 354831 | - | 260 | 0.64 (0.4, 1.04) | 0.075 | 0.62 (0.49, 0.78) | 6.76 × 10−05 | 0.73 (0.62, 0.86) | 1.70 × 10−04 |
Body mass index: by height and weight measurement | 359983 | - | 260 | 0.67 (0.42, 1.08) | 0.104 | 0.63 (0.49, 0.79) | 8.47 × 10−05 | 0.76 (0.65, 0.89) | 9.52 × 10−04 |
Family History | |||||||||
Father with AD/dementia | 312666 | 15022 | 3 | 0.38 (0.13, 1.07) | 0.068 | 0.39 (0.34, 0.44) | 2.59 × 10−50 | - | - |
Mather with AD/dementia | 331041 | 28507 | 5 | 0.41 (0.23, 0.72) | 0.002 | 0.45 (0.39, 0.51) | 1.14 × 10−33 | 0.46 (0.26, 0.81) | 5.88 × 10−04 |
Father with heart disease | 318570 | 104110 | 19 | 0.29 (0.11, 0.77) | 0.013 | 0.49 (0.34, 0.71) | 1.46 × 10−04 | 0.48 (0.29, 0.79) | 9.74 × 10−04 |
Siblings with heart disease | 280784 | 28696 | 3 | 0.33 (0.03, 4.21) | 0.391 | 0.44 (0.28, 0.68) | 2.59 × 10−04 | - | - |
Siblings with high blood pressure | 281619 | 58495 | 15 | 0.37 (0.06, 2.38) | 0.296 | 0.72 (0.48, 1.07) | 0.101 | 0.57 (0.26, 1.23) | 0.006 |
Siblings with none of group 1 disease* | 281979 | 190969 | 5 | 34.04 (0.24, 4912.96) | 0.164 | 3.3 (1.62, 6.73) | 9.92 × 10−04 | 3.27 (0.89, 12.04) | 0.023 |
Medication | |||||||||
Aspirin | 361141 | 48081 | 6 | 0.17 (0.04, 0.85) | 0.031 | 0.34 (0.22, 0.52) | 9.03 × 10−07 | 0.35 (0.15, 0.84) | 0.001 |
Atorvastatin | 361141 | 10805 | 18 | 0.48 (0.23, 0.99) | 0.048 | 0.74 (0.65, 0.84) | 4.67 × 10−06 | 0.64 (0.02, 18.99) | 0.006 |
Amlodipine | 361141 | 14588 | 18 | 0.63 (0.33, 1.22) | 0.173 | 0.68 (0.57, 0.82) | 3.08 × 10−05 | 0.71 (0.24, 2.06) | 3.17 × 10−04 |
Metformin | 361141 | 8968 | 31 | 0.94 (0.81, 1.09) | 0.427 | 0.92 (0.84, 1.01) | 0.092 | 0.89 (0.46, 1.74) | 5.03 × 10−04 |
Simvastatin | 361141 | 40921 | 33 | 0.72 (0.41, 1.27) | 0.261 | 0.74 (0.6, 0.9) | 0.003 | 0.65 (0.36, 1.15) | 2.89 × 10−04 |
Bendroflumethiazide | 361141 | 20196 | 32 | 0.46 (0.27, 0.8) | 0.006 | 0.67 (0.58, 0.78) | 2.02 × 10−07 | 0.7 (0.45, 1.09) | 1.00 × 10−06 |
Blood pressure medication (females) | 193148 | 33519 | 76 | 0.8 (0.59, 1.08) | 0.148 | 0.74 (0.66, 0.83) | 1.84 × 10−07 | 0.72 (0.66, 0.8) | 2.49 × 10−10 |
Blood pressure medication (males) | 165340 | 40987 | 56 | 0.67 (0.45, 1) | 0.050 | 0.73 (0.63, 0.83) | 5.22 × 10−06 | 0.69 (0.62, 0.77) | 1.30 × 10−08 |
Cholesterol lowering medication (females) | 193148 | 24247 | 28 | 0.77 (0.51, 1.15) | 0.198 | 0.81 (0.7, 0.94) | 0.006 | 0.74 (0.48, 1.14) | 9.27 × 10−04 |
Cholesterol lowering medication (males) | 165340 | 38057 | 38 | 0.69 (0.5, 0.95) | 0.024 | 0.81 (0.69, 0.94) | 0.007 | 0.74 (0.59, 0.91) | 1.54 × 10−04 |
None of medication taken (females) | 193148 | 133338 | 28 | 1.26 (0.48, 3.35) | 0.641 | 1.72 (1.34, 2.21) | 1.94 × 10−05 | 1.52 (1.1, 2.1) | 0.001 |
None of medication taken (males) | 165340 | 110372 | 49 | 1.43 (0.85, 2.42) | 0.179 | 1.46 (1.23, 1.74) | 2.16 × 10−05 | 1.53 (1.33, 1.76) | 1.56 × 10−06 |
Early life factors | |||||||||
Comparative height size at age 10 | 355331 | - | 225 | 0.69 (0.43, 1.1) | 0.122 | 0.81 (0.63, 1.03) | 0.088 | 0.77 (0.65, 0.92) | 0.004 |
Education | |||||||||
College or University degree | 357549 | 115981 | 189 | 1.12 (0.72, 1.74) | 0.616 | 1.29 (1.14, 1.47) | 9.95 × 10−05 | 1.17 (1, 1.36) | 0.003 |
Lifestyle | |||||||||
Age first had sexual intercourse | 317694 | - | 136 | 1.65 (0.52, 5.16) | 0.394 | 1.74 (1.28, 2.38) | 4.59 × 10−04 | 1.64 (1.32, 2.05) | 2.35 × 10−05 |
Diet | |||||||||
Never eat sugar or foods/drinks containing sugar | 359777 | 67292 | 14 | 0.18 (0.02, 1.34) | 0.093 | 0.62 (0.42, 0.91) | 0.016 | 0.59 (0.31, 1.11) | 0.003 |