Multi-omic profiling of Metabolome and Epigenome Signature Related with OP Exposure

Abstract

TPS 911: Air pollution, epigenetics, biomarkers, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background: Organophosphates (OP) are widely used insecticides that have been associated with a wide range of adverse health outcomes. There is great interest in improving the understanding of molecular mechanisms related to chronic OP exposure induced toxicity. We aim to integrate metabolomics and epigenomics to investigate the pathophysiologic response related with OP exposure on system biology level. Methods: In a population-based case control study of Parkinson’s disease (PD), we assessed ambient OP exposure via residential and workplace proximity to commercial applications. We investigated associations between OP exposure and serum metabolome (LC/MS) as well as genome-wide DNA methylation (Illumina 450 k) in 99 blood samples (79 PD patients, 20 controls). Weighted gene coexpression network analysis (WGCNA) was used to identify modules of correlated CpG sites and metabolites. A partial correlation network was constructed from the modules and the relations between the module network and the OP exposure were investigated. Results: Epigenomic modules associated with OP exposure were enriched in pathways related with acetylcholine and other neurotransmitters’ activity. The associations between OP exposure and oxidative stress and inflammation were observed in both metabolomic and epigenomic profiles. The epigenomic and metabolomic modules were interrelated and showed cross-sectional associations with OP exposure. Conclusion: Long-term OP exposure associates with both metabolome and epigenome. By integrating metabolomics and epigenomics, we illustrated that OP exposure could disrupt neurotransmission, and induce oxidative stress and inflammation, which could then increase the risk of adverse health outcomes.