Metabolomics of Lead Exposure and Its Role in Respiratory Disease
Abstract
The overarching hypothesis of this proposal was that exposure to lead (Pb) during active military service is related to the observed high prevalence of poor lung health among veterans. We aimed to explore the mechanisms underlying this relationship utilizing metabolomics; i.e. the systematic profiling of small (<10kDa) metabolites in a biological sample, which will allow us to construct a causal pathway demonstrating the mechanistic and biological connections between Pb exposure and lung health. To achieve this aim we identified participants from the ongoing Normative Ageing Study of Veterans. We selected men with detailed histories on their exposure to Pb, with comprehensive data on long term lung health and with blood samples suitable for metabolomics profiling. We identified 661 plasma samples from 464 veterans, which we shipped to Metabolon Inc. for metabolomic profiling using four LCMS platforms, enabling the broadest coverage of the metabolome possible. We applied QC and data processing pipelines to these data and created the Normative Aging Study Metabolomics Cohort. To date, we have successfully identified a metabolomic profile associated with Pb exposure and a metabolomic profile associated with poor lung health. Our analyses, encompassing both frequentist and network approaches, suggested that the relationship between Pb and the lung is mediated, in part, by dysregulated xanthine metabolism; leucine, isoleucine and valine Metabolism; lipids and aceylated amino acids. These findings have been presented at both national and international conferences, and have resulted in one published manuscript, one under submission, and one pending submission. In addition, we have initiated two new research avenues utilizing the metabolomics data generated as part of this project one focused on metabolomics and air pollution (three manuscripts currently under review) and the other on metabolomics and mental health, in the Normative Aging Study Metabolomics Cohort.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2020
- Accession Number
- AD1152355
Entities
People
- Jessica Lasky-Su
- Rachel S Kelly
Organizations
- Brigham and Women's Hospital