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Get Free AccessAbstract DNA methylation (DNAm) is a developmentally dynamic epigenetic process, yet we still know little about how epigenetic effects on health outcomes vary over time; whether DNAm alterations during certain periods of development are more informative than others; and whether epigenetic timing effects differ by outcome. To address these questions, we applied longitudinal meta-regression to published meta-analyses from the PACE consortium that examine DNAm at multiple time points (prospectively at birth and cross-sectionally in childhood) in relation to the same child outcome (ADHD, general psychopathology, sleep, BMI, asthma). Our findings reveal three new insights: (i) across outcomes, effects sizes are larger when DNAm is measured in childhood compared to at birth; (ii) higher effect sizes do not necessarily translate into more significant findings, as associations also become noisier in childhood for most outcomes (i.e. showing larger standard errors); and (iii) DNAm signals are highly time-specific while showing pleiotropy across health outcomes.
Alexander Neumann, Sara Sammallahti, Marta Cosín‐Tomás, Sarah E. Reese, Matthew Suderman, Silvia Alemany, Catarina Almqvist, Sandra Andrušaitytė, Syed Hasan Arshad, Marian J. Bakermans‐Kranenburg, Lawrence J. Beilin, Carrie V. Breton, Mariona Bustamante, Darina Czamara, Dana Dabelea, Celeste Eng, Brenda Eskenazi, Bernard F. Fuemmeler, Frank D. Gilliland, Regina Gražulevičienė, Siri E. Håberg, Gunda Herberth, Nina Holland, Amy Hough, Donglei Hu, Karen Huen, Anke Hüls, Jianping Jin, Jordi Júlvez, Berthold Koletzko, Gerard H. Koppelman, Inger Kull, Xueling Lu, Léa Maître, Dan Mason, Erik Melén, Simon Kebede Merid, Peter L. Molloy, Trevor A. Mori, Rosa H. Mulder, Christian M. Page, Rebecca C. Richmond, Stefan Röder, Jason P. Ross, Laura Schellhas, Sylvain Sebért, Dean Sheppard, Harold Snieder, Anne P. Starling, Dan Joseph Stein, Gwen Tindula, Marinus H. van IJzendoorn, Judith M. Vonk, Esther Walton, Jonathan Witonsky, Cheng‐Jian Xu, Ivana V. Yang, Paul Yousefi, Heather J. Zar, Ana Claudia Zenclussen, Hongmei Zhang, Henning Tiemeier, Stephanie J. London, Janine F. Felix, Charlotte A. M. Cecil (2024). Epigenetic timing effects on child developmental outcomes: A longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium. , DOI: https://doi.org/10.1101/2024.02.29.24303506.
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Type
Preprint
Year
2024
Authors
65
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1101/2024.02.29.24303506
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