Evidence map›Paper›PMID 42304632›Full record

SynthesisJournal of child psychology and psychiatry, and allied disciplines2026

Childhood internalising symptoms at ages 3 and 6: a meta-analysis of epigenome-wide associations from cord and peripheral blood.

Laura Schellhas, Mannan Luo, Janine F Felix, Christian M Page, Mona Bekkhus, Marcus R Munafò, Luisa Zuccolo, Alexandra Havdahl, Charlotte A M Cecil, Gemma C Sharp

Abstract readMeta-Analysis
In one paragraph

Synthesis in Journal of child psychology and psychiatry, and allied disciplines, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

10 authors.

Laura SchellhasSchool of Psychological Science, University of Bristol, Bristol, UK.ORCID https://orcid.org/0000-0001-6436-4821
Mannan LuoDepartment of Child & Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Janine F FelixThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Christian M PageDivision for Mental and Physical Health, Department of Physical Health and Aging, Norwegian Institute of Public Health, Oslo, Norway.
Mona BekkhusDepartment of Psychology, PROMENTA Research Centre, University of Oslo, Oslo, Norway.
Marcus R MunafòSchool of Psychological Science, University of Bristol, Bristol, UK.
Luisa ZuccoloMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Alexandra HavdahlResearch Department, Lovisenberg Diaconal Hospital, Oslo, Norway.
Charlotte A M CecilDepartment of Child & Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.ORCID https://orcid.org/0000-0002-2389-5922
Gemma C SharpMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

Funding

Alan Turing InstituteData and Connectivity National Core StudyEuropean Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL, NutriPROGRAM project, UK MRC MR/S036520/1European Research Council 101039672European Union's Horizon 2020 research and innovation programme 101057390European Union's Horizon 2020 research and innovation programme 101057529European Union's Horizon 2020 research and innovation programme 721567European Union's Horizon 2020 research and innovation programme 848158Health Data Science Centre, Fondazione Human Technopole, Milan, ItalyHevolution/AFAR New Investigator Awardee in Aging Biology and Geroscience ResearchMRC New Investigator Research MR/S009310/1MRC New Investigator Research MR/W020297/1South-Eastern Norway Regional Health Authority 2020022the Research Council of Norway 288083the Research Council of Norway 301004
6 · The paper itself

Abstract

backgroundPre- 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.

methodsWe 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.

resultsNo 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.

conclusionsThe 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.

Indexed as

Behavioral SymptomsDNA MethylationEpigenomeFetal BloodChildChild, PreschoolFemaleGenome-Wide Association StudyHumansDNA methylationinternalising problemsPACE consortium

Identifiers

PMID42304632
PMCPMC13647090

What Socratic holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.