期刊
EPIGENOMICS
卷 9, 期 3, 页码 253-265出版社
FUTURE MEDICINE LTD
DOI: 10.2217/epi-2016-0145
关键词
DNA methylation; mediation analysis; misclassification
资金
- Intramural Research Program of NIH, National Institute of Environmental Health Sciences (NIEHS)
- Norwegian Ministry of Health
- Ministry of Education and Research, NIH/NIEHS [N01-ES-75558, ZO1 ES-49019]
- NIH/NINDS [1 UO1 NS 047537-01]
- Norwegian Research Council/FUGE [151918/S10]
- Norwegian Research Council/BIOBANK [221097]
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.
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