Epigenetic timing effects on child developmental outcomes: A longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium

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.