Title: Application of an analytical framework for multivariate mediation analysis of environmental data.
Authors: Aung, Max T; Song, Yanyi; Ferguson, Kelly K; Cantonwine, David E; Zeng, Lixia; McElrath, Thomas F; Pennathur, Subramaniam; Meeker, John D; Mukherjee, Bhramar
Published In Nat Commun, (2020 11 06)
Abstract: Diverse toxicological mechanisms may mediate the impact of environmental toxicants (phthalates, phenols, polycyclic aromatic hydrocarbons, and metals) on pregnancy outcomes. In this study, we introduce an analytical framework for multivariate mediation analysis to identify mediation pathways (q = 61 mediators) in the relationship between environmental toxicants (p = 38 analytes) and gestational age at delivery. Our analytical framework includes: (1) conducting pairwise mediation for unique exposure-mediator combinations, (2) exposure dimension reduction by estimating environmental risk scores, and (3) multivariate mediator analysis using either Bayesian shrinkage mediation analysis, population value decomposition, or mediation pathway penalization. Dimension reduction demonstrates that a one-unit increase in phthalate risk score is associated with a total effect of 1.07 lower gestational age (in weeks) at delivery (95% confidence interval: 0.48-1.67) and eicosanoids from the cytochrome p450 pathway mediated 26% of this effect (95% confidence interval: 4-63%). Eicosanoid products derived from the cytochrome p450 pathway may be important mediators of phthalate toxicity.
PubMed ID: 33159049
MeSH Terms: Adult; Environmental Exposure/adverse effects; Environmental Pollutants/toxicity*; Female; Gestational Age; Humans; Infant, Newborn; Male; Maternal Exposure/adverse effects*; Phenols/toxicity; Phthalic Acids/toxicity; Polycyclic Aromatic Hydrocarbons/toxicity; Pregnancy; Pregnancy Outcome