Misclassified exposure in epigenetic mediation analyses. Does DNA methylation mediate effects of smoking on birthweight?. (March 2017)

• Record Type: Journal Article
• Authors: Valeri, Linda; Reese, Sarah L; Zhao, Shanshan; Page, Christian M; Nystad, Wenche; Coull, Brent A; London, Stephanie J
• Is Part Of: Epigenomics. Volume 9:Number 3(2017)
• Page Start: 253
• Page End: 265
• Publication Date: 2017-03
• Subjects: DNA methylation -- mediation analysis -- misclassification; Epigenesis -- Periodicals; Genomics -- Periodicals; Chromatin -- Periodicals; DNA -- Periodicals; 572.87
• DOI: 10.2217/epi-2016-0145
• Languages: English
• ISSNs: 1750-1911

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.