Epigenetic timing effects on child developmental outcomes: a longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium
Rattachement africain : nl, fi, es, us, gb, se, lt, pt, au, de, no, Afrique du Sud, cl, ca. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
BACKGROUND: DNA methylation (DNAm) is a developmentally dynamic epigenetic process; yet, most epigenome-wide association studies (EWAS) have examined DNAm at only one timepoint or without systematic comparisons between timepoints. Thus, it is unclear whether DNAm alterations during certain developmental periods are more informative than others for health outcomes, how persistent epigenetic signals are across time, and whether epigenetic timing effects differ by outcome. METHODS: We applied longitudinal meta-regression models to published meta-analyses from the PACE consortium that examined DNAm at two timepoints-prospectively at birth and cross-sectionally in childhood-in relation to the same child outcome (ADHD symptoms, general psychopathology, sleep duration, BMI, asthma). These models allowed systematic comparisons of effect sizes and statistical significance between timepoints. Furthermore, we tested correlations between DNAm regression coefficients to assess the consistency of epigenetic signals across time and outcomes. Finally, we performed robustness checks, estimated between-study heterogeneity, and tested pathway enrichment. RESULTS: Our findings reveal three new insights: (i) across outcomes, DNAm effect sizes are consistently larger in childhood cross-sectional analyses compared to prospective analyses at birth; (ii) higher effect sizes do not necessarily translate into more significant findings, as associations also become noisier in childhood for most outcomes (showing larger standard errors in cross-sectional vs prospective analyses); and (iii) DNAm signals are highly time-specific, while also showing evidence of shared associations across health outcomes (ADHD symptoms, general psychopathology, and asthma). Notably, these observations could not be explained by sample size differences and only partly to differential study-heterogeneity. DNAm sites changing associations were enriched for neural pathways. CONCLUSIONS: Our results highlight developmentally-specific associations between DNAm and child health outcomes, when assessing DNAm at birth vs childhood. This implies that EWAS results from one timepoint are unlikely to generalize to another. Longitudinal studies with repeated epigenetic assessments are direly needed to shed light on the dynamic relationship between DNAm, development and health, as well as to enable the creation of more reliable and generalizable epigenetic biomarkers. More broadly, this study underscores the importance of considering the time-varying nature of DNAm in epigenetic research and supports the potential existence of epigenetic "timing effects" on child health.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Epigenetic timing effects on child developmental outcomes: a longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium
- Date Crossref
- 14/04/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Erasmus MC pays non établi dans la noticeÉtablissement de santé
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Erasmus University Rotterdam pays non établi dans la noticeUniversité ou école supérieure
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University of Helsinki Department of Obstetrics and Gynecology pays non établi dans la noticeUniversité ou école supérieure
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Helsinki University Hospital pays non établi dans la noticeÉtablissement de santé
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Universitat Pompeu Fabra pays non établi dans la noticeUniversité ou école supérieure
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Barcelona Institute for Global Health pays non établi dans la noticeÉtablissement de santé
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Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública pays non établi dans la noticeStructure de recherche
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Westat (United States) pays non établi dans la noticeEntreprise
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At Bristol pays non établi dans la noticeOrganisation à but non lucratif
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University of Bristol Population Health Sciences pays non établi dans la noticeUniversité ou école supérieure
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Vall d'Hebron Institut de Recerca pays non établi dans la noticeStructure de recherche
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Vall d'Hebron Hospital Universitari pays non établi dans la noticeÉtablissement de santé
Erasmus MC, Erasmus University Rotterdam et Department of Obstetrics and Gynecology — University of Helsinki, avec 9 autres affiliations. Pays d’affiliation : Afrique du Sud.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.