DNA methylation links prenatal smoking exposure to later life health outcomes in offspring

Petri Wiklund, Ville Karhunen, Rebecca C. Richmond, Priyanka Parmar, Alina Rodriguez, Maneka De Silva, Matthias Wielscher, Faisal I. Rezwan, Tom G. Richardson, Juha Veijola, Karl Heinz Herzig, John W. Holloway, Caroline L. Relton, Sylvain Sebert, Marjo Riitta Järvelin*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

9 Citations (Scopus)
173 Downloads (Pure)

Abstract

Background: Maternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship.Methods: We examined the association of prenatal maternal smoking with offspring blood DNA methylation in 2,821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess, whether methylation markers have causal effects on disease outcomes in the offspring.Results: We identify 69 differentially methylated CpGs in 36 genomic regions (P < 1×10-7) associated with exposure to maternal smoking in adolescents and adults. Mendelian randomization analyses provided evidence for a causal role of four maternal smoking related CpG sites on an increased risk of inflammatory bowel diseases or schizophrenia. Further mediation analyses showed some evidence of cg25189904 in GNG12 gene mediating the effect of exposure to maternal smoking on schizophrenia-related outcomes. Conclusions: DNA methylation may represent a biological mechanism through which maternal smoking is associated with increased risk of psychiatric morbidity in the exposed offspring.
Original languageEnglish
Article number97
Number of pages16
JournalClinical Epigenetics
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Jul 2019

Structured keywords

  • ICEP

Keywords

  • maternal smoking
  • pregnancy
  • DNA methylation
  • persistence
  • mediation
  • disease
  • causality
  • lifecourse

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