Gaussian graphical modeling of the serum exposome and metabolome reveals interactions between environmental chemicals and endogenous metabolites.
- Author(s): Bessonneau, Vincent
- Gerona, Roy R
- Trowbridge, Jessica
- Grashow, Rachel
- Lin, Thomas
- Buren, Heather
- Morello-Frosch, Rachel
- Rudel, Ruthann A
- et al.
Published Web Locationhttps://doi.org/10.1038/s41598-021-87070-9
Given the complex exposures from both exogenous and endogenous sources that an individual experiences during life, exposome-wide association studies that interrogate levels of small molecules in biospecimens have been proposed for discovering causes of chronic diseases. We conducted a study to explore associations between environmental chemicals and endogenous molecules using Gaussian graphical models (GGMs) of non-targeted metabolomics data measured in a cohort of California women firefighters and office workers. GGMs revealed many exposure-metabolite associations, including that exposures to mono-hydroxyisononyl phthalate, ethyl paraben and 4-ethylbenzoic acid were associated with metabolites involved in steroid hormone biosynthesis, and perfluoroalkyl substances were linked to bile acids-hormones that regulate cholesterol and glucose metabolism-and inflammatory signaling molecules. Some hypotheses generated from these findings were confirmed by analysis of data from the National Health and Nutrition Examination Survey. Taken together, our findings demonstrate a novel approach to discovering associations between chemical exposures and biological processes of potential relevance for disease causation.