1546

Background/Aim Pyrethroid pesticide use is increasing worldwide, although the full extent of associated health effects is unknown. An epigenome-wide analysis study (EWAS) with exploratory pathway analysis may help identify potential pyrethroid-related health effects.Methods We performed an EWAS of chronic ambient pyrethroid exposure using control participants’ blood in the Parkinson’s Environment and Genes Study in California (N=237). We estimated associations of exposure to ambient pyrethroid pesticide applications in the 5 years prior to enrollment with differential methylation at enrollment, using beta regression and an FDR q <0.05 for significance. We normalized methylation values for typeI/II probe bias using BMIQ, evaluated batch effects with SVA, and adjusted for cell count. We also performed gene set overrepresentation analysis on the genes annotated to CpG sites that were associated with pyrethroids at a raw p-value cutoff of 0.05. For gene-set overrepresentation analyses, we controlled for background counts of CpG sites on the Illumina450K chip, and identified Gene Ontology (GO) biological process terms with missMethyl, and OMIM and Glad4U disease-associated gene sets. We used an FDR q< 0.05 to evaluate statistical significance of gene sets. Results 5 CpG sites were differentially methylated in relation to pyrethroid exposures. Two of these sites annotated to genes involved in calcium ion binding, a known primary target of pyrethroid pesticides. We also identified 40 GO terms, 14 of which were neurological/developmental in nature. For disease sets, we identified signals for Alzheimer’s disease, leukemia and several other cancers, diabetes, birth defects, and other diseases. Conclusions Chronic ambient pyrethroid exposure is associated with differential methylation at CpG sites that annotate to a wide variety of disease states and biological mechanisms. While several of the identified diseases and gene processes are consistent with prior research, this EWAS also implicates several previously unidentified diseases for future investigation in relation to pyrethroid exposure.

2568

Background: Organophosphates (OP) are widely used insecticides that acutely inhibit acetylcholinesterase enzyme activity. There is great interest in improving the understanding of molecular mechanisms related to chronic OP exposure induced toxicity. We aim to elucidate metabolomic changes associated with OP exposure using high-resolution metabolomics (HRM).Methods: In a population-based case control study of Parkinson's disease (PD), we retrieved serum samples of 178 controls and assessed ambient OP exposure via residential and workplace proximity to commercial applications for each subject. We used liquid chromatography-high resolution mass spectrometry to obtain untargeted metabolic profiles and partial least squares regression to select metabolic features associated with OP exposure. Pathway analyses were employed to identify biologic pathways related to OP exposure. Confounders including age, race/ethnicity, sex were controlled a prior.Results: In total we extracted 8,615 and 4,124 metabolic features from serum samples in hydrophilic interaction (HILIC) chromatography (positive ion mode) and C18 (negative ion mode) columns, respectively. Controlling for confounding factors, 151 and 50 discriminatory metabolic features (HILIC and C18, respectively) were selected (Variable Importance in Projection (VIP) >= 2). Pathway enrichment analysis for discriminatory features associated with OP indicated that in serum fatty acid oxidation and inflammation related pathways were altered, including arachidonic acid, leukotriene, and prostaglandin pathways.Conclusion: This study finds chronic low-level OP exposure is associated with differential metabolomic profiles in serum. Our study results suggest that long-term sub-acute OP exposure influences metabolites enriched for oxidative stress and inflammation pathways.

1964

The upcoming NASA Multi-Angle Imager for Aerosols (MAIA) investigation seeks to extend NASA’s capabilities to study the impact of different size and compositional mixtures of particulate matter (PM) on adverse health outcomes. The MAIA satellite instrument, in development at the Jet Propulsion Laboratory and planned for launch in mid-2022, will collect multiangular, multispectral, and polarimetric measurements over a set of globally distributed target areas. Retrievals of aerosol properties will be combined with ground-based monitor data and chemical transport modeling to produce 1-km gridded data products of daily-averaged PM₁₀ and PM_2.5 mass, as well as the fractional abundances of sulfate, nitrate, organic carbon, elemental carbon, and dust making up the retrieved PM_2.5 mixtures. Epidemiologists on the MAIA Science Team and their collaborators will use these data in studies aimed at associating health risk with particle types. The MAIA Early Adopters Program is designed to engage the wider air quality and public health communities and assist them in using MAIA data products, which will be publicly available, free of charge, from NASA’s Atmospheric Science Data Center. This presentation will cover the plans for operational MAIA data products as well as test data products that will be available prior to launch, and opportunities for Early Adopters to become involved in the program.