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

Sara Sammallahti (1, 2) , M. Elisabeth Koopman-Verhoeff (2) , Anne-Claire Binter (3, 4, 5) , Rosa Mulder (2) , Alba Cabré-Riera (3, 4, 5) , Tuomas Kvist (6) , Anni Malmberg (6) , Giancarlo Pesce (7) , Sabine Plancoulaine (8) , Jonathan Heiss (9) , Sheryl Rifas-Shiman (10) , Stefan Röder (11) , Anne Starling (12, 13) , Rory Wilson (14) , Kathrin Guerlich (15) , Kristine Haftorn (16) , Christian Page (17, 18) , Annemarie Luik (2) , Henning Tiemeier (2, 19) , Janine Felix (2) , Katri Raikkonen (6) , Jari Lahti (6) , Caroline Relton (20) , Gemma Sharp (20) , Melanie Waldenberger (21) , Veit Grote (15) , Barbara Heude (8) , Isabella Annesi‐maesano (22) , Marie-France Hivert (10) , Ana C Zenclussen (23) , Gunda Herberth (23) , Dana Dabelea (24) , Regina Grazuleviciene (25) , Marina Vafeiadi (26) , Siri Håberg (17) , Stephanie London (27) , Mònica Guxens (2, 3, 5, 4) , Rebecca Richmond (20) , Charlotte Cecil (2, 28, 29)

1 HUS - Helsinki University Hospital [Finland]
2 Erasmus MC - Erasmus University Medical Center [Rotterdam]
3 ISGlobal - Instituto de Salud Global - Institute For Global Health [Barcelona]
4 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
5 UPF - Universitat Pompeu Fabra [Barcelona]
6 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
7 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
8 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
9 UPCité - Université Paris Cité
10 HMS - Harvard Medical School [Boston]
11 Department Community Ecology [UFZ Leipzig]
12 UNC - University of North Carolina [Chapel Hill]
13 University of Colorado [Colorado Springs]
14 German Research Center for Environmental Health - Helmholtz Center München (GmbH)
15 Dr von Hauner Children's Hospital [Munich, Germany]
16 UiO - University of Oslo
17 NIPH - Norwegian Institute of Public Health [Oslo]
18 Oslo University Hospital [Oslo]
19 Harvard University
20 University of Bristol [Bristol]
21 Helmholtz Zentrum München = German Research Center for Environmental Health
22 IDESP - Institut Desbrest de santé publique
23 UFZ - Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research
24 University of Colorado - Department of Applied Mathematics
25 VDU - Vytautas Magnus University - Vytauto Didziojo Universitetas
26 UOC - University of Crete [Heraklion]
27 NIH - National Institutes of Health [Bethesda, MD, USA]
28 LUMC - Leiden University Medical Center
29 King‘s College London

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.

Mots clés: Sleep; Methylation; Epigenomics; Actigraphy; Child; Meta‑analysis; Longitudinal studies

Domaines: Sciences du Vivant [q-bio]

Sara Sammallahti, M. Elisabeth Koopman-Verhoeff, Anne-Claire Binter, Rosa Mulder, Alba Cabré-Riera, et al.. Longitudinal associations of DNA methylation and sleep in children: a meta-analysis. Clinical Epigenetics, 2022, 14 (1), pp.83. ⟨10.1186/s13148-022-01298-4⟩. ⟨hal-04099381⟩