A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation

Giulietta S Monasso, Thanh T Hoang, Giulia Mancano, Sílvia Fernández-Barrés, John Dou, Vincent W V Jaddoe, Christian M Page, Laura Johnson, Mariona Bustamante, Kelly M Bakulski, Siri E Håberg, Per M Ueland, Thomas Battram, Simon K Merid, Erik Melén, Doretta Caramaschi, Leanne K Küpers, Jordi Sunyer, Wenche Nystad, Sandra G HeilRebecca J Schmidt, Martine Vrijheid, Gemma C Sharp, Stephanie J London, Janine F Felix*

*Corresponding author for this work

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

2 Citations (Scopus)

Abstract

Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy ( n  = 2,420) or cord blood ( n  = 1,029), with cord blood DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at 109 and 7 CpGs, respectively (False Discovery Rate P-value <0.05). Persistent associations with DNA methylation in the peripheral blood of up to 482 children aged 4-10 y were observed for 40.7% of CpGs associated with maternal vitamin B12 and 57.1% of CpGs associated with newborn vitamin B12. Of the CpGs identified in the maternal meta-analyses, 4.6% were associated with either birth weight or gestational age in a previous work. For the newborn meta-analysis, this was the case for 14.3% of the identified CpGs. Also, of the CpGs identified in the newborn meta-analysis, 14.3% and 28.6%, respectively, were associated with childhood cognitive skills and nonverbal IQ. Of the 109 CpGs associated with maternal vitamin B12, 18.3% were associated with nearby gene expression. In this study, we showed that maternal and newborn vitamin B12 concentrations are associated with DNA methylation at multiple CpGs in offspring blood ( P FDR<0.05). Whether this differential DNA methylation underlies associations of vitamin B12 concentrations with child health outcomes, such as birth weight, gestational age, and childhood cognition, should be further examined in future studies.

Original languageEnglish
Article number2202835
JournalEpigenetics
Volume18
Issue number1
DOIs
Publication statusPublished - 24 Apr 2023

Bibliographical note

Funding Information:
The work was supported by the Medical Research Council [MR/S009310/1]; European Research Council [ERC-2014-CoG-648916]. For all studies, acknowledgements can be found in Supplementary Information: Acknowledgements. For all studies, funding statements can be found in Supplementary Information: Funding.

Publisher Copyright:
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • Infant, Newborn
  • Pregnancy
  • Child
  • Female
  • Humans
  • DNA Methylation
  • Epigenome
  • Birth Weight/genetics
  • Vitamin B 12/metabolism
  • Epigenesis, Genetic
  • Fetal Blood/metabolism

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