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  4. A multivariate approach to investigate the combined biological effects of multiple exposures
 
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A multivariate approach to investigate the combined biological effects of multiple exposures
File(s)
564.full.pdf (2.32 MB)
Published version
Author(s)
Chadeau, M
Jain, P
Vineis, P
Liquet, Benoit
Vlaanderen, Jelle
more
Type
Journal Article
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 multi-level extension of the 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 high-dimensional 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.
Date Issued
2018-07-01
Date Acceptance
2018-02-19
Citation
Journal of Epidemiology and Community Health, 2018, 72, pp.564-571
URI
http://hdl.handle.net/10044/1/57297
DOI
https://www.dx.doi.org/10.1136/jech-2017-210061
ISSN
0143-005X
Publisher
BMJ Publishing Group
Start Page
564
End Page
571
Journal / Book Title
Journal of Epidemiology and Community Health
Volume
72
Copyright Statement
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/
Sponsor
Commission of the European Communities
Cancer Research UK
Grant Number
308610
‘Mechanomics’ PRC project grant 22184
Subjects
OMICs data
exposome
multi-level sparse PLS models
multiple exposures
multivariate response
1117 Public Health And Health Services
1604 Human Geography
Epidemiology
Publication Status
Published
Date Publish Online
2018-03-21
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