Application of an analytical framework for multivariate mediation analysis of environmental data

Max T. Aung, Yanyi Song, Kelly K. Ferguson, David E. Cantonwine, Lixia Zeng, Thomas F. McElrath, Subramaniam Pennathur, John D. Meeker and Bhramar Mukherjee ()
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Max T. Aung: University of Michigan School of Public Health
Yanyi Song: University of Michigan School of Public Health
Kelly K. Ferguson: Research Triangle Park
David E. Cantonwine: Brigham and Women’s Hospital, Harvard Medical School
Lixia Zeng: University of Michigan
Thomas F. McElrath: Brigham and Women’s Hospital, Harvard Medical School
Subramaniam Pennathur: University of Michigan
John D. Meeker: University of Michigan School of Public Health
Bhramar Mukherjee: University of Michigan School of Public Health

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19335-2

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DOI: 10.1038/s41467-020-19335-2

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