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

Sara Sammallahti, M Elisabeth Koopman-Verhoeff, Anne-Claire Binter*, Rosa H Mulder, Alba Cabré-Riera, Tuomas Kvist, Anni L K Malmberg, Giancarlo Pesce, Sabine Plancoulaine, Jonathan A Heiss, Sheryl L Rifas-Shiman, Stefan W Röder, Anne P Starling, Rory Wilson, Kathrin Guerlich, Kristine L Haftorn, Christian M Page, Annemarie I Luik, Henning Tiemeier, Janine F FelixKatri Raikkonen, Jari Lahti, Caroline L Relton, Gemma C Sharp, Melanie Waldenberger, Veit Grote, Barbara Heude, Isabella Annesi-Maesano, Marie-France Hivert, Ana C Zenclussen, Gunda Herberth, Dana Dabelea, Regina Grazuleviciene, Marina Vafeiadi, Siri E Håberg, Stephanie J London, Mònica Guxens, Rebecca C Richmond, Charlotte A M Cecil

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)
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Abstract

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 × 10 -8). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10 -8, n = 577) and sleep onset latency (p = 8.8 × 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.

Original languageEnglish
Article number83
Number of pages12
JournalClinical Epigenetics
Volume14
Issue number1
DOIs
Publication statusPublished - 5 Jul 2022

Bibliographical note

Funding Information:
Acknowledgements for each of the participating studies are listed in Additional file 2 : Methods. This is the first meta-analysis of DNA methylation and child sleep. This study has several methodological strengths, including the harmonized epigenome-wide approach, large sample size, rich parent-reported and actigraphy-based sleep data, and the analysis of both prospective and cross-sectional associations between DNA methylation and sleep. We show that there are no consistent associations of DNA methylation measured from cord blood at birth, or DNA methylation measured from peripheral blood in childhood, and parent-reported sleep duration, sleep initiation problems or fragmentation. Interestingly, however, we identify associations between DNA methylation and actigraphy-based sleep duration and sleep onset latency. This suggests that these objectively measured sleep outcomes could be of particular interest, as we disentangle the basic biological mechanisms responsible for differences in sleep.

Publisher Copyright:
© 2022, The Author(s).

Keywords

  • DNA Methylation
  • Epigenesis, Genetic
  • Epigenome
  • Humans
  • Sleep/genetics
  • Sleep Wake Disorders/genetics

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