Longitudinal associations of DNA methylation and sleep in children: a meta-analysis

Background Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children. Methods We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4-13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration. Results We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 x 10(-8)). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 x 10(-8), n = 577) and sleep onset latency (p = 8.8 x 10(-9), n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716-2539). Conclusion DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available.