Application of an analytical framework for multivariate mediation analysis of environmental data.
Max T AungYanyi SongKelly K FergusonDavid E CantonwineLixia ZengThomas F McElrathSubramaniam PennathurJohn D MeekerBhramar MukherjeePublished in: Nature communications (2020)
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.
Keyphrases
- gestational age
- social support
- birth weight
- human health
- preterm birth
- polycyclic aromatic hydrocarbons
- pregnancy outcomes
- data analysis
- risk assessment
- life cycle
- depressive symptoms
- pregnant women
- liquid chromatography
- oxidative stress
- machine learning
- big data
- physical activity
- drinking water
- mass spectrometry
- weight loss
- heavy metals
- health risk