Epigenetic timing effects on child developmental outcomes: A longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium
Neumann, A.; Sammallahti, S.; Cosin-Tomas, M.; Reese, S. E.; Suderman, M.; Alemany, S.; Almqvist, C.; Andrusaityte, S.; Arshad, S. H.; Bakermans-Kranenburg, M. J.; Beilin, L.; Breton, C.; Bustamante, M.; Czamara, D.; Dabelea, D.; Eng, C.; Eskenazi, B.; Fuemmeler, B. F.; Gilliland, F. D.; Grazuleviciene, R.; Haberg, S. E.; Herberth, G.; Holland, N.; Hough, A.; Hu, D.; Huen, K.; Hüls, A.; Jin, J.; Julvez, J.; Koletzko, B. V.; Koppelman, G. H.; Kull, I.; Lu, X.; Maitre, L.; Mason, D.; Melen, E.; Merid, S. K.; Molloy, P. L.; Mori, T. A.; Mulder, R. H.; Page, C. M.; Richmond, R. C.; Roder, S.; Ros
Show abstract
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.
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