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Table 1 Sensitivity analysis results for the metabolites identified in primary analysis

From: Investigating causal relationships between exposome and human longevity: a Mendelian randomization 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
  1. *Group 1: heart disease, stroke, high blood pressure, chronic bronchitis/emphysema, Alzheimer's disease/dementia, and diabetes
  2. AD Alzheimer’s disease, COPD chronic obstructive pulmonary diseases, CI confidence interval, DVT deep venous thrombosis, MR-PRESSO Mendelian randomization pleiotropy residual sum and outlier, IVW inverse variance weighted method, OR odds ratio, SNP single nucleotide polymorphisms