DNA methylation mediates the effect of maternal smoking during pregnancy on birthweight of the offspring

Leanne K. Kupers*, Xiaojing Xu, Soesma A. Jankipersadsing, Ahmad Vaez, Sacha la Bastide-van Gemert, Salome Scholtens, Ilja M. Nolte, Rebecca C. Richmond, Caroline L. Relton, Janine F. Felix, Liesbeth Duijts, Joyce B. van Meurs, Henning Tiemeier, Vincent W. Jaddoe, Xiaoling Wang, Eva Corpeleijn, Harold Snieder

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background: We examined whether the effect of maternal smoking during pregnancy on birthweight of the offspring was mediated by smoking-induced changes to DNA methylation in cord blood.

Methods: First, we used cord blood of 129 Dutch children exposed to maternal smoking vs 126 unexposed to maternal and paternal smoking (53% male) participating in the GECKO Drenthe birth cohort. DNA methylation was measured using the Illumina HumanMethylation450 Beadchip. We performed an epigenome-wide association study for the association between maternal smoking and methylation followed by a mediation analysis of the top signals [false-discovery rate (FDR)

Results: We found 35 differentially methylated CpGs (FDR

Conclusions: Maternal smoking during pregnancy was associated with cord blood methylation differences. We observed a potentially mediating role of methylation in the association between maternal smoking during pregnancy and birthweight of the offspring. Functional network analysis suggested a role in activating the immune system.

Original languageEnglish
Pages (from-to)1224-1237
Number of pages14
JournalInternational Journal of Epidemiology
Volume44
Issue number4
DOIs
Publication statusPublished - Aug-2015

Keywords

  • Epigenetic epidemiology
  • epigenome-wide association study
  • DOHaD
  • fetal programming
  • GECKO
  • ALSPAC
  • Generation R
  • GENE-EXPRESSION
  • PRESCHOOL-CHILDREN
  • TOBACCO-SMOKE
  • CORD BLOOD
  • EXPOSURE
  • COHORT
  • ASSOCIATION
  • RISK
  • IDENTIFICATION
  • AUTOIMMUNITY

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