A multivariate approach to investigate the combined biological effects of multiple exposures

Pooja Jain, Paolo Vineis, Benoît Liquet, Jelle Vlaanderen, Barbara Bodinier, Karin van Veldhoven, Manolis Kogevinas, Toby J. Athersuch, Laia Font-Ribera, Cristina M. Villanueva, Roel Vermeulen, Marc Chadeau-Hyam*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Epidemiological studies provide evidence that environmental exposures may affect health through complex mixtures. Formal investigation of the effect of exposure mixtures is usually achieved by modelling interactions, which relies on strong assumptions relating to the identity and the number of the exposures involved in such interactions, and on the order and parametric form of these interactions. These hypotheses become difficult to formulate and justify in an exposome context, where influential exposures are numerous and heterogeneous. To capture both the complexity of the exposome and its possibly pleiotropic effects, models handling multivariate predictors and responses, such as partial least squares (PLS) algorithms, can prove useful. As an illustrative example, we applied PLS models to data from a study investigating the inflammatory response (blood concentration of 13 immune markers) to the exposure to four disinfection by-products (one brominated and three chlorinated compounds), while swimming in a pool. To accommodate the multiple observations per participant (n=60; before and after the swim), we adopted a multilevel extension of PLS algorithms, including sparse PLS models shrinking loadings coefficients of unimportant predictors (exposures) and/or responses (protein levels). Despite the strong correlation among co-occurring exposures, our approach identified a subset of exposures (n=3/4) affecting the exhaled levels of 8 (out of 13) immune markers. PLS algorithms can easily scale to highdimensional exposures and responses, and prove useful for exposome research to identify sparse sets of exposures jointly affecting a set of (selected) biological markers. Our descriptive work may guide these extensions for higher dimensional data.

Original languageEnglish
Pages (from-to)564-571
Number of pages8
JournalJournal of Epidemiology and Community Health
Volume72
Issue number7
DOIs
Publication statusPublished - Jul 2018
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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