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Table 2 The significant adjusted associations between long-term (annual) exposure to PM2.5 with metabolomics (multi-pollutant models) at ENT95% significance level

From: Metabolomic signatures of the long-term exposure to air pollution and temperature

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

  1. 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
  2. Beta (SE) and p-values presented are from individual metabolites analysis
  3. 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
  4. Significant metabolites at ENT95% significance level only are presented
  5. 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
  6. 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
  7. 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)
  8. 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
  9. *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
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Environmental Health

ISSN: 1476-069X