Misclassified exposure in epigenetic mediation analyses. Does DNA methylation mediate effects of smoking on birthweight?
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ABSTRACT: Aims
Assessing whether epigenetic alterations mediate associations between environmental exposures and health outcomes is increasingly popular. We investigate the impact of exposure misclassification in such investigations.Materials & methods
We quantify bias and false-positive rates due to exposure misclassification in mediation analysis and assess the performance of the simulation extrapolation method (SIMEX). We evaluate whether DNA-methylation mediates smoking-birth weight relationship in the Norwegian Mother and Child Study birth cohort.Results
Ignoring exposure misclassification increases type I error in mediation analysis. The direct effect is underestimated and, when the mediator is a biomarker of the exposure, as is true for smoking, the indirect effect is overestimated.Conclusion
Misclassification correction plus cautious interpretation are recommended for mediation analyses in the presence of exposure misclassification.
SUBMITTER: Valeri L
PROVIDER: S-EPMC5331915 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Publications
Misclassified exposure in epigenetic mediation analyses. Does DNA methylation mediate effects of smoking on birthweight?
Valeri Linda L Reese Sarah L SL Zhao Shanshan S Page Christian M CM Nystad Wenche W Coull Brent A BA London Stephanie J SJ
Epigenomics 20170221 3
<h4>Aims</h4>Assessing whether epigenetic alterations mediate associations between environmental exposures and health outcomes is increasingly popular. We investigate the impact of exposure misclassification in such investigations.<h4>Materials & methods</h4>We quantify bias and false-positive rates due to exposure misclassification in mediation analysis and assess the performance of the simulation extrapolation method (SIMEX). We evaluate whether DNA-methylation mediates smoking-birth weight re ...[more]
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