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. During this reporting period, 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 initiated the statistical analysis plan outlined in our proposal. 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 Glycine, Serine and Threonine Metabolism; Histidine Metabolism; Leucine, Isoleucine and Valine Metabolism; Phospholipid Metabolism and Sphingolipid metabolism. These findings have been accepted for presentation at the American Thoracic Society Annual conference, and during the next reporting period we aim to publish these initial findings, complete construction of the causal pathway and move toward biomarker development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2018
- Accession Number
- AD1093872
Entities
People
- Jessica Lasky-Su
- Rachel S Kelly
Organizations
- Brigham and Women's Hospital