Epigenetic timing effects on child developmental outcomes: A longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium
Author:
Neumann AlexanderORCID, Sammallahti Sara, Cosin-Tomas MartaORCID, Reese Sarah EORCID, Suderman Matthew, Alemany Silvia, Almqvist Catarina, Andrusaityte Sandra, Arshad Syed HORCID, Bakermans-Kranenburg Marian JORCID, Beilin Lawrence, Breton Carrie, Bustamante Mariona, Czamara DarinaORCID, Dabelea Dana, Eng Celeste, Eskenazi Brenda, Fuemmeler Bernard F, Gilliland Frank D, Grazuleviciene Regina, Håberg Siri E, Herberth GundaORCID, Holland Nina, Hough Amy, Hu Donglei, Huen Karen, Hüls AnkeORCID, Jin Jianping, Julvez Jordi, Koletzko Berthold V, Koppelman Gerard HORCID, Kull IngerORCID, Lu Xueling, Maitre Léa, Mason Dan, Melén Erik, Merid Simon K, Molloy Peter L, Mori Trevor A, Mulder Rosa H, Page Christian M, Richmond Rebecca C, Röder Stefan, Ross Jason P, Schellhas LauraORCID, Sebert SylvainORCID, Sheppard Dean, Snieder Harold, Starling Anne P, Stein Dan JORCID, Tindula Gwen, van IJzendoorn Marinus H, Vonk Judith, Walton Esther, Witonsky Jonathan, Xu Cheng-JianORCID, Yang Ivana V, Yousefi Paul DORCID, Zar Heather J, Zenclussen Ana CORCID, Zhang Hongmei, Tiemeier Henning, London Stephanie JORCID, Felix Janine F, Cecil CharlotteORCID
Abstract
AbstractDNA 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.
Publisher
Cold Spring Harbor Laboratory
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