Childhood internalising symptoms at ages 3 and 6

A meta‐analysis of epigenome‐wide associations from cord and peripheral blood

Bibliographic Data

ID21344184
AuthorsLaura Schellhas (0000-0001-6436-4821, School of Psychological Science University of Bristol Bristol UK), Mannan Luo (0000-0003-3923-2362, Department of Child & Adolescent Psychiatry/Psychology, Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands), Janine F Felix (The Generation R Study Group, Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands), Christian M Page (Division for Mental and Physical Health, Department of Physical Health and Aging Norwegian Institute of Public Health Oslo Norway), Mona Bekkhus (0000-0002-4447-8909, Department of Psychology, PROMENTA Research Centre University of Oslo Oslo Norway), Marcus R Munafò (School of Psychological Science University of Bristol Bristol UK), Luisa Zuccolo (0000-0002-7049-3037, MRC Integrative Epidemiology Unit University of Bristol Bristol UK), Alexandra Havdahl (0000-0002-9268-0423, Research Department Lovisenberg Diaconal Hospital Oslo Norway), Charlotte A M Cecil (0000-0002-2389-5922, Department of Child & Adolescent Psychiatry/Psychology, Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands), Gemma C Sharp (0000-0003-2906-4035, MRC Integrative Epidemiology Unit University of Bristol Bristol UK)
Year2026
Publication date2026-06-16
Open AccessYes
TypeARTICLE
VenueJournal of Child Psychology and Psychiatry (JOURNAL)
Journal identifiersISSN: 0021-9630 • E-ISSN: 1469-7610
PublisherWiley (PUBLISHER • GB)
DOI10.1111/jcpp.70186
PMID42304632
OpenAlexW7165022368
LanguageEN
References cited86

BACKGROUND: Pre- and postpartum environments and genetic effects influence childhood internalising problems, which increase depression risk. DNA methylation (DNAm) may capture some of these effects. We therefore investigated associations between child blood DNAm and internalising problems. METHODS: We meta-analysed probe and region-level epigenome-wide association studies using data from 3 European birth cohorts (ALSPAC, MoBa, Generation R; analytic N = 1,121-3,011) from the Pregnancy And Childhood Epigenetics (PACE) Consortium. DNAm was assessed at birth (cord blood) and age 6 years (peripheral blood). Internalising problems (ages 3 and 6) were reported by mothers using the Child Behaviour Checklist or Strengths and Difficulties Questionnaire. Models were adjusted for age at DNAm assessment, 20 surrogate variables, estimated cell proportions, maternal education, age, smoking and, in secondary analysis, maternal anxiety and depression. Public databases were searched for mental health associations with top CpG sites and regions. RESULTS: No significant probe-level associations were found between cord- or peripheral-blood DNAm and internalising problems. In region-level analyses, two differentially methylated regions (DMRs) in cord blood were associated with internalising problems at age 3 (annotated to STK32C, MIR886) and one at age 6 (PFKFB2). At age 6, peripheral-blood analyses identified two DMRs (C10orf26 (WBP1L), FAM125A). Several genes showed prior associations with psychiatric phenotypes, including depression. CONCLUSIONS: The higher-powered regional-level analyses revealed more associations than probe-level. Among others, we identified a region annotated to STK32C that has previously been linked to adolescent depression. Larger samples and refined phenotyping are needed to clarify the role of DNAm in internalising problems

Anxiety · Cord blood · CpG site · DNA methylation · dNaM · Epigenetics · Generation R · Mental health · Pregnancy · Digital Mental Health Interventions · Epigenetics and DNA Methylation · Mental Health via Writing

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