Epigenome-wide associations between observed maternal sensitivity and offspring DNA methylation: a population-based prospective study in children

Lorenza Dall'Aglio, Jolien Rijlaarsdam, Rosa Mulder, Alexander Neumann, Janine Felix, Rianne Kok, MJ Bakermans-Kranenburg, Marinus van IJzendoorn, Henning Tiemeier, Charlotte Cecil

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Abstract

Background. Experimental work in animals has shown that DNA methylation (DNAm), an epigenetic mechanism regulating gene expression, is influenced by typical variation in maternal care. While emerging research in humans supports a similar association, studies to date have been limited to candidate gene and cross-sectional approaches, with a focus on extreme deviations in the caregiving environment. Methods. Here, we explored the prospective association between typical variation in maternal sensitivity and offspring epigenome-wide DNAm, in a population-based cohort of children (N = 235). Maternal sensitivity was observed when children were 3- and 4-years-old. DNAm, quantified with the Infinium 450 K array, was extracted at age 6 (whole blood). The influence of methylation quantitative trait loci (mQTLs), DNAm at birth (cord blood), and confounders (socioeconomic status, maternal psychopathology) was considered in follow-up analyses. Results. Genome-wide significant associations between maternal sensitivity and offspring DNAm were observed at 13 regions (p < 1.06 × 10-07), but not at single sites. Follow-up analyses indicated that associations at these regions were in part related to genetic factors, confounders, and baseline DNAm levels at birth, as evidenced by the presence of mQTLs at five regions and estimate attenuations. Robust associations with maternal sensitivity were found at four regions, annotated to ZBTB22, TAPBP, ZBTB12, and DOCK4. Conclusions. These findings provide novel leads into the relationship between typical variation in maternal caregiving and offspring DNAm in humans, highlighting robust regions of associations, previously implicated in psychological and developmental problems, immune functioning, and stress responses.

Original languageEnglish
Pages (from-to)2481-2491
Number of pages11
JournalPsychological Medicine
Volume52
Issue number13
DOIs
Publication statusPublished - 3 Oct 2022

Bibliographical note

Publisher Copyright:
© The Author(s), 2020. Published by Cambridge University Press.

Research programs

  • EMC MM-04-54-08-A
  • ESSB PED

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