Application of high-resolution metabolomics in the CHDWB cohort to identify biological pathways perturbed by traffic-related air pollution Pubblico

Abstract

Purpose

To identify metabolic perturbations associated with short-term exposures to ambient traffic-related air pollutants (TRAP), including carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O­3), fine particulate matter (PM2.5), organic carbon (OC), and elemental carbon (EC) among a subset of participants in the Center for Health Discovery and Well-Being (CHDWB), a cohort of Emory University employees.

Methods

A cross-sectional study was conducted on baseline visits of 180 CHDWB participants whose plasma samples that had undergone untargeted high-resolution metabolomics (HRM) profiling using liquid chromatography-high-resolution mass spectrometry with positive and negative electrospray ionization modes. Ambient pollution concentrations were measured at an ambient monitor near downtown Atlanta and assigned to each participant according to their date of visit. Metabolic variations associated with pollution exposures were assessed following a metabolome-wide association study framework, considering both Tobit models and regular multiple linear regression models with adjustment of temporal covariates to identify significant metabolic features. Enriched biological pathways, i.e., those perturbed by pollution, were then identified by Mummichog.

Results

The study population was predominantly white (76.1%) and non-smokers (95.6%). All participants has at least a high school education. In total, 7,821 and 4,123 metabolic features were extracted from the plasma samples by the negative and positive ion mode runs, respectively. After removing features present in less than 10% of participants, 7,106 and 3,628 remains. Biological pathways enriched by metabolic features associated with the pollutants of interest primarily pertained to nucleotide metabolism (e.g., pyrimidine metabolism, which was associated with CO, NO2, EC, and OC), lipid metabolism, and amino acid metabolism. NO2 and EC were associated most consistently with these pathways.

Conclusions

We identified a range of ambient pollutants, including components of TRAP, associated with changes to the metabolic phenotype among the cohort. The results demonstrate the use of HRM as a viable platform for untargeted characterization of molecular mechanisms underlying exposure to TRAP.

Table of Contents

Table of Contents

Introduction.. 1

Methods. 4

Results. 8

Discussion. 9

Conclusions and Recommendations. 15

References. 17

Tables and Figures. 26

Appendices. 37

About this Master's Thesis

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School	Rollins School of Public Health
Department	Environmental Health
Degree	M.S.P.H.
Submission	Master's Thesis
Language	English
Research Field	Environmental Health Health Sciences, Public Health
Parola chiave	Biological pathways High resolution metabolomics Metabolic perturbations Traffic-related air pollution
Committee Chair / Thesis Advisor	Stefanie Sarnat, Emory University
Committee Members	Donghai Liang, Emory University

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