Table 2.
The significant adjusted associations between long-term (annual) exposure to PM2.5 with metabolomics (multi-pollutant models) at ENT95% significance level
| BIOCHEMICAL | Super-Pathway | Sub-Pathway | Beta (SE) for individual metabolites | P-value for individual metabolites | ICA_factor2 Weight | ICA_factor2 Rank |
|---|---|---|---|---|---|---|
| Aspartate | Amino Acid | Alanine and Aspartate Metabolism | − 0.203 (0.046) | 1.93E-05 | 0.392 | 57 |
| Cys-Gly, Oxidized | Amino Acid | Glutathione Metabolism | −0.357 (0.060) | 1.10E-08 | 0.527 | 19 |
| Cysteinylglycine Disulfide* | Amino Acid | Glutathione Metabolism | −0.316 (0.051) | 4.00E-09 | 0.434 | 43 |
| Cysteinylglycine | Amino Acid | Glutathione Metabolism | −0.361 (0.059) | 7.00E-09 | 0.266 | 115 |
| Sarcosine | Amino Acid | Glycine, Serine and Threonine Metabolism | 0.293 (0.051) | 4.60E-08 | 0.094 | 291 |
| Alpha-Hydroxyisocaproate | Amino Acid | Leucine, Isoleucine and Valine Metabolism | −0.266 (0.051) | 5.69E-07 | 0.483 | 27 |
| Taurine | Amino Acid | Methionine, Cysteine, SAM and Taurine Metabolism | −0.190 (0.040) | 3.79E-06 | 0.423 | 45 |
| Cysteine S-Sulfate | Amino Acid | Methionine, Cysteine, SAM and Taurine Metabolism | −0.580 (0.075) | 6.76E-13 | 0.412 | 50 |
| 5-Methylthioadenosine (MTA) | Amino Acid | Polyamine Metabolism | 0.222 (0.052) | 2.77E-05 | −0.277 | 108 |
| Maltose | Carbohydrate | Glycogen Metabolism | −0.321 (0.065) | 1.90E-06 | 0.536 | 17 |
| 3-Phosphoglycerate | Carbohydrate | Glycolysis, Gluconeogenesis, and Pyruvate Metabolism | −0.499 (0.067) | 3.33E-12 | 0.856 | 2 |
| Lactate | Carbohydrate | Glycolysis, Gluconeogenesis, and Pyruvate Metabolism | −0.233 (0.044) | 3.54E-07 | 0.448 | 39 |
| Ribitol | Carbohydrate | Pentose Metabolism | −0.278 (0.065) | 2.68E-05 | 0.204 | 152 |
| Heme | Cofactors and Vitamins | Hemoglobin and Porphyrin Metabolism | −0.348 (0.073) | 3.34E-06 | 0.599 | 10 |
| Bilirubin (E,Z Or Z,E)* | Cofactors and Vitamins | Hemoglobin and Porphyrin Metabolism | 0.354 (0.066) | 2.93E-07 | −0.327 | 79 |
| Bilirubin (E,E)* | Cofactors and Vitamins | Hemoglobin and Porphyrin Metabolism | 0.343 (0.062) | 1.30E-07 | −0.260 | 118 |
| Bilirubin (Z,Z) | Cofactors and Vitamins | Hemoglobin and Porphyrin Metabolism | 0.381 (0.059) | 1.00E-09 | −0.117 | 243 |
| Nicotinamide | Cofactors and Vitamins | Nicotinate and Nicotinamide Metabolism | −0.237 (0.049) | 3.27E-06 | 0.515 | 22 |
| Alpha-Tocopherol | Cofactors and Vitamins | Tocopherol Metabolism | 0.279 (0.055) | 8.57E-07 | −0.121 | 233 |
| Malate | Energy | TCA Cycle | −0.164 (0.038) | 2.93E-05 | 0.311 | 90 |
| Succinate | Energy | TCA Cycle | −0.161 (0.037) | 2.72E-05 | 0.249 | 127 |
| 1-Stearoyl-GPS (18:0)* | Lipid | Lysophospholipid | −0.31 (0.069) | 1.30E-05 | 0.640 | 7 |
| 1-Arachidonoyl-GPA (20:4) | Lipid | Lysophospholipid | −0.282 (0.065) | 2.40E-05 | 0.462 | 34 |
| 1,2-Dipalmitoyl-GPE (16:0/16:0)* | Lipid | Phosphatidylethanolamine (PE) | −0.299 (0.068) | 1.79E-05 | 0.406 | 52 |
| 1-Stearoyl-2-Oleoyl-GPS (18:0/18:1) | Lipid | Phosphatidylserine (PS) | −0.264 (0.061) | 2.55E-05 | 0.640 | 8 |
| Phosphoethanolamine | Lipid | Phospholipid Metabolism | −0.228 (0.049) | 4.92E-06 | 0.552 | 14 |
| Sphinganine | Lipid | Sphingolipid Synthesis | −0.249 (0.049) | 9.96E-07 | 0.530 | 18 |
| Sphingomyelin (D18:2/18:1)* | Lipid | Sphingomyelins | 0.137 (0.032) | 2.88E-05 | −0.066 | 423 |
| Sphingosine | Lipid | Sphingosines | −0.249 (0.049) | 1.17E-06 | 0.562 | 13 |
| Inosine 5′-Monophosphate (IMP) | Nucleotide | Purine Metabolism, (Hypo)Xanthine/Inosine containing | −0.423 (0.076) | 1.02E-07 | 0.799 | 3 |
| Hypoxanthine | Nucleotide | Purine Metabolism, (Hypo)Xanthine/Inosine containing | −0.327 (0.073) | 1.33E-05 | 0.755 | 5 |
| Allantoin | Nucleotide | Purine Metabolism, (Hypo)Xanthine/Inosine containing | −0.229 (0.043) | 3.45E-07 | 0.012 | 1007 |
| Adenosine 5′-Monophosphate (AMP) | Nucleotide | Purine Metabolism, Adenine containing | −0.433 (0.066) | 4.16E-10 | 0.797 | 4 |
| Dihydroorotate | Nucleotide | Pyrimidine Metabolism, Orotate containing | 0.356 (0.066) | 2.41E-07 | −0.279 | 106 |
| Uracil | Nucleotide | Pyrimidine Metabolism, Uracil containing | −0.284 (0.064) | 1.40E-05 | 0.399 | 56 |
| Beta-Alanine | Nucleotide | Pyrimidine Metabolism, Uracil containing | −0.149 (0.035) | 2.87E-05 | 0.214 | 147 |
| Gamma-Glutamylmethionine | Peptide | Gamma-glutamyl Amino Acid | 0.324 (0.049) | 2.84E-10 | −0.384 | 60 |
| Gamma-Glutamylalanine | Peptide | Gamma-glutamyl Amino Acid | 0.347 (0.07) | 1.41E-06 | −0.360 | 65 |
| Gamma-Glutamylglycine | Peptide | Gamma-glutamyl Amino Acid | 0.35 (0.047) | 2.76E-12 | −0.290 | 100 |
| Gamma-Glutamylglutamine | Peptide | Gamma-glutamyl Amino Acid | 0.22 (0.042) | 4.59E-07 | −0.250 | 125 |
| Gamma-Glutamylvaline | Peptide | Gamma-glutamyl Amino Acid | 0.216 (0.047) | 7.33E-06 | −0.229 | 138 |
| Gamma-Glutamylisoleucine* | Peptide | Gamma-glutamyl Amino Acid | 0.197 (0.046) | 2.64E-05 | −0.205 | 151 |
| Gamma-Glutamyl-Alpha-Lysine | Peptide | Gamma-glutamyl Amino Acid | 0.207 (0.04) | 7.56E-07 | −0.192 | 162 |
| Gamma-Glutamylthreonine | Peptide | Gamma-glutamyl Amino Acid | 0.152 (0.036) | 3.03E-05 | −0.077 | 351 |
| Iminodiacetate (IDA) | Xenobiotics | Chemical | 0.352 (0.049) | 2.51E-11 | −0.125 | 227 |
| Hepes | Xenobiotics | Chemical | 0.874 (0.154) | 4.90E-08 | 0.062 | 447 |
| Tartronate (Hydroxymalonate) | Xenobiotics | Food Component/Plant | 0.238 (0.047) | 1.19E-06 | −0.442 | 41 |
| Ergothioneine | Xenobiotics | Food Component/Plant | −0.213 (0.046) | 7.84E-06 | 0.268 | 112 |
| X - 24,970 | Un-identified | – | −0.389 (0.072) | 2.01E-07 | 0.360 | 63 |
| X - 24,307 | Un-identified | – | 0.512 (0.068) | 3.06E-12 | −0.340 | 74 |
| X - 23,739 | Un-identified | – | 0.266 (0.056) | 3.36E-06 | − 0.337 | 76 |
| X - 12,104 | Un-identified | – | 0.349 (0.056) | 4.00E-09 | −0.319 | 84 |
| X - 11,632 | Un-identified | – | −0.329 (0.052) | 2.00E-09 | 0.318 | 85 |
| X - 13,684 | Un-identified | – | −0.383 (0.077) | 1.55E-06 | 0.317 | 86 |
| X - 24,306 | Un-identified | – | 0.397 (0.059) | 1.57E-10 | −0.165 | 184 |
| X - 24,431 | Un-identified | – | −0.334 (0.063) | 3.10E-07 | 0.160 | 190 |
| X - 14,904 | Un-identified | – | −0.327 (0.063) | 6.26E-07 | −0.119 | 237 |
| X - 10,458 | Un-identified | – | −0.303 (0.059) | 8.90E-07 | 0.022 | 865 |
These models were linear mixed-effect regression models (LMEM) with random participant-specific intercepts and simultaneously adjusted for PM2.5, NO2, O3, and temperature (multi-pollutant models) for the same exposure window
Beta (SE) and p-values presented are from individual metabolites analysis
All models were adjusted for age (years), body mass index (kg/m2), cigarette pack-years, alcohol intake (< or ≥ 2 drinks per day), socioeconomic status (income payment and years of education), season (warm/cold), and relative humidity
Significant metabolites at ENT95% significance level only are presented
ICA_factor2 rank represents the rank of the corresponding metabolite contributing to factor 2 from the independent component analysis (ICA). Higher rank (and higher weights) means higher contribution to factor 2 of the ICA. We show alongside the weights and ranks of each metabolite that contributes to factor 2 from the ICA only because it was the only significant factor
Range of facto2- ICA rank is from 1 to 1158 i.e., number of examined metabolites. Range of facto2- ICA weight is from − 1 to 1
The metabolites with an X-XXXX format are unknown (to date Metabolon has not been able to name the metabolite) but reproducible (Metabolon is reliably able to characterize this metabolite in multiple samples and studies)
Abbreviations: ENT Effective/independent number of tests, PM2.5 Particulate matter ≤2.5 μm, NO2 Nitrogen dioxide, and O3 Ozone, ICA Independent component analysis, SE Standard error
*Indicates a compound that has not been confirmed based on a standard, but Metabolon is confident in its identity based on a subset of these analytical parameters