Evidence map›Paper›PMID 38600394›Full record

ArticleCellular and molecular life sciences : CMLS2024

Sex differences in DNA methylation across gestation: a large scale, cross-cohort, multi-tissue analysis.

Darina Czamara, Linda Dieckmann, Marius Lahti-Pulkkinen, Cristiana Cruceanu, Wolfgang Henrich, Andreas Plagemann, Katri Räikkönen, Thorsten Braun, Elisabeth B Binder, Jari Lahti and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. NewbornGenes · 2025
    Pooled it
  2. Review
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  9. Effects of positive mGlu5 modulation on DJournal of psychopharmacology (Oxford, England) · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 5 countries.

Darina CzamaraDepartment Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany. darina@psych.mpg.de.ORCID http://orcid.org/0000-0001-7381-904X
Linda DieckmannDepartment Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany.ORCID http://orcid.org/0000-0002-1050-0098
Marius Lahti-PulkkinenDepartment of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-5244-5525
Cristiana CruceanuDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-7799-5531
Wolfgang HenrichDepartment of Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-0759-832X
Andreas PlagemannDepartment of Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin, Germany.
Katri RäikkönenDepartment of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0003-3124-3470
Thorsten Braun *Department of Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin, Germany.
Elisabeth B Binder *Department Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany.ORCID http://orcid.org/0000-0001-7088-6618
Jari Lahti *Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-4310-5297
Sonja Entringer *Institute of Medical Psychology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin, Germany. sonja.entringer@charite.de.ORCID http://orcid.org/0000-0002-9926-7076
Humboldt-Universität zu Berlin · DEUniversity of Helsinki · FIMax Planck Institute of Psychiatry · DEEmory University · USKarolinska Institutet · SEUniversity of California, Irvine · US

Funding

Academy of Finland 128789Academy of Finland 1287891Academy of Finland 1312670Academy of Finland 269925Academy of Finland 311617Academy of Finland 330206Academy of Finland 336209Deutsche Forschungsgemeinschaft -2Deutsche Forschungsgemeinschaft 241/8-2Deutsche Forschungsgemeinschaft 2925/3-1Deutsche Forschungsgemeinschaft -3
6 · The paper itself

Abstract

Biological sex is a key variable influencing many physiological systems. Disease prevalence as well as treatment success can be modified by sex. Differences emerge already early in life and include pregnancy complications and adverse birth outcomes. The placenta is a critical organ for fetal development and shows sex-based differences in the expression of hormones and cytokines. Epigenetic regulation, such as DNA methylation (DNAm), may underlie the previously reported placental sexual dimorphism. We associated placental DNAm with fetal sex in three cohorts. Individual cohort results were meta-analyzed with random-effects modelling. CpG-sites differentially methylated with sex were further investigated regarding pathway enrichment, overlap with methylation quantitative trait loci (meQTLs), and hits from phenome-wide association studies (PheWAS). We evaluated the consistency of findings across tissues (CVS, i.e. chorionic villus sampling from early placenta, and cord blood) as well as with gene expression. We identified 10,320 epigenome-wide significant sex-differentially methylated probes (DMPs) spread throughout the epigenome of the placenta at birth. Most DMPs presented with lower DNAm levels in females. DMPs mapped to genes upregulated in brain, were enriched for neurodevelopmental pathways and significantly overlapped with meQTLs and PheWAS hits. Effect sizes were moderately correlated between CVS and placenta at birth, but only weakly correlated between birth placenta and cord blood. Sex differential gene expression in birth placenta was less pronounced and implicated genetic regions only marginally overlapped with those associated with differential DNAm. Our study provides an integrative perspective on sex-differential DNAm in perinatal tissues underscoring the possible link between placenta and brain.

Indexed as

DNA MethylationPlacentaEpigenesis, GeneticFemaleFetal DevelopmentHumansInfant, NewbornMalePregnancySex CharacteristicsCVSDNA methylationEpigeneticsPlacentaSex

Identifiers

PMID38600394
PMCPMC11006734
OpenAlexW4394676423

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.