Misclassified Exposure in Epigenetic Mediation Analyses. Does DNA Methylation Mediate Effects of Smoking on Birthweight?

Overview

Journal Epigenomics

Specialty Genetics

Date 2017 Feb 25

PMID 28234025

Citations 31

Authors

Linda Valeri

Sarah L Reese

Shanshan Zhao

Christian M Page

Wenche Nystad

Brent A Coull

Stephanie J London

Affiliations

Soon will be listed here.

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.

Citing Articles

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An examination of mediation by DNA methylation on birthweight differences induced by assisted reproductive technologies.

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