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

被引：38

作者：

Valeri, Linda ^{[1
,2
]}

Reese, Sarah L. ^{[3
]}

Zhao, Shanshan ^{[3
]}

Page, Christian M. ^{[4
]}

Nystad, Wenche ^{[4
]}

Coull, Brent A. ^{[5
]}

London, Stephanie J. ^{[3
]}

机构：

[1] Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA

[2] McLean Hosp, Psychiatr Biostat Lab, Belmont, MA 02478 USA

[3] NIH, Nat Inst Environm Hlth Sci, Dept Hlth & Human Serv, Res Triangle Pk, NC USA

[4] Nat Inst Publ Hlth, Oslo, Norway

[5] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA

来源：

EPIGENOMICS | 2017年 / 9卷 / 03期

关键词：

DNA methylation; mediation analysis; misclassification; MATERNAL SMOKING; CIGARETTE-SMOKING; MEASUREMENT ERROR; GESTATIONAL-AGE; NEWBORNS; PREGNANCY; BIOMARKER; VARIABLES;

D O I：

10.2217/epi-2016-0145

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：253 / 265

页数：13

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