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 Felix; Katri 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

doi:10.1186/s13148-022-01298-4

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

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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 language	English
Article number	83
Number of pages	12
Journal	Clinical Epigenetics
Volume	14
Issue number	1
DOIs	https://doi.org/10.1186/s13148-022-01298-4
Publication status	Published - 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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Sammallahti, S., Koopman-Verhoeff, M. E., Binter, A.-C., Mulder, R. H., Cabré-Riera, A., Kvist, T., Malmberg, A. L. K., Pesce, G., Plancoulaine, S., Heiss, J. A., Rifas-Shiman, S. L., Röder, S. W., Starling, A. P., Wilson, R., Guerlich, K., Haftorn, K. L., Page, C. M., Luik, A. I., Tiemeier, H., ... Cecil, C. A. M. (2022). Longitudinal associations of DNA methylation and sleep in children: a meta-analysis. Clinical Epigenetics, 14(1), Article 83. https://doi.org/10.1186/s13148-022-01298-4

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title = "Longitudinal associations of DNA methylation and sleep in children: a meta-analysis",

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.",

keywords = "DNA Methylation, Epigenesis, Genetic, Epigenome, Humans, Sleep/genetics, Sleep Wake Disorders/genetics",

author = "Sara Sammallahti and Koopman-Verhoeff, {M Elisabeth} and Anne-Claire Binter and Mulder, {Rosa H} and Alba Cabr{\'e}-Riera and Tuomas Kvist and Malmberg, {Anni L K} and Giancarlo Pesce and Sabine Plancoulaine and Heiss, {Jonathan A} and Rifas-Shiman, {Sheryl L} and R{\"o}der, {Stefan W} and Starling, {Anne P} and Rory Wilson and Kathrin Guerlich and Haftorn, {Kristine L} and Page, {Christian M} and Luik, {Annemarie I} and Henning Tiemeier and Felix, {Janine F} and Katri Raikkonen and Jari Lahti and Relton, {Caroline L} and Sharp, {Gemma C} and Melanie Waldenberger and Veit Grote and Barbara Heude and Isabella Annesi-Maesano and Marie-France Hivert and Zenclussen, {Ana C} and Gunda Herberth and Dana Dabelea and Regina Grazuleviciene and Marina Vafeiadi and H{\aa}berg, {Siri E} and London, {Stephanie J} and M{\`o}nica Guxens and Richmond, {Rebecca C} and Cecil, {Charlotte A M}",

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: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = jul,

day = "5",

doi = "10.1186/s13148-022-01298-4",

language = "English",

volume = "14",

journal = "Clinical Epigenetics",

issn = "1868-7075",

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number = "1",

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Sammallahti, S, Koopman-Verhoeff, ME, Binter, A-C, Mulder, RH, Cabré-Riera, A, Kvist, T, Malmberg, ALK, Pesce, G, Plancoulaine, S, Heiss, JA, Rifas-Shiman, SL, Röder, SW, Starling, AP, Wilson, R, Guerlich, K, Haftorn, KL, Page, CM, Luik, AI, Tiemeier, H, Felix, JF, Raikkonen, K, Lahti, J, Relton, CL, Sharp, GC, Waldenberger, M, Grote, V, Heude, B, Annesi-Maesano, I, Hivert, M-F, Zenclussen, AC, Herberth, G, Dabelea, D, Grazuleviciene, R, Vafeiadi, M, Håberg, SE, London, SJ, Guxens, M, Richmond, RC & Cecil, CAM 2022, 'Longitudinal associations of DNA methylation and sleep in children: a meta-analysis', Clinical Epigenetics, vol. 14, no. 1, 83. https://doi.org/10.1186/s13148-022-01298-4

TY - JOUR

T1 - Longitudinal associations of DNA methylation and sleep in children

T2 - a meta-analysis

AU - Sammallahti, Sara

AU - Koopman-Verhoeff, M Elisabeth

AU - Binter, Anne-Claire

AU - Mulder, Rosa H

AU - Cabré-Riera, Alba

AU - Kvist, Tuomas

AU - Malmberg, Anni L K

AU - Pesce, Giancarlo

AU - Plancoulaine, Sabine

AU - Heiss, Jonathan A

AU - Rifas-Shiman, Sheryl L

AU - Röder, Stefan W

AU - Starling, Anne P

AU - Wilson, Rory

AU - Guerlich, Kathrin

AU - Haftorn, Kristine L

AU - Page, Christian M

AU - Luik, Annemarie I

AU - Tiemeier, Henning

AU - Felix, Janine F

AU - Raikkonen, Katri

AU - Lahti, Jari

AU - Relton, Caroline L

AU - Sharp, Gemma C

AU - Waldenberger, Melanie

AU - Grote, Veit

AU - Heude, Barbara

AU - Annesi-Maesano, Isabella

AU - Hivert, Marie-France

AU - Zenclussen, Ana C

AU - Herberth, Gunda

AU - Dabelea, Dana

AU - Grazuleviciene, Regina

AU - Vafeiadi, Marina

AU - Håberg, Siri E

AU - London, Stephanie J

AU - Guxens, Mònica

AU - Richmond, Rebecca C

AU - Cecil, Charlotte A M

N1 - 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).

PY - 2022/7/5

Y1 - 2022/7/5

N2 - 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.

AB - 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.

KW - DNA Methylation

KW - Epigenesis, Genetic

KW - Epigenome

KW - Humans

KW - Sleep/genetics

KW - Sleep Wake Disorders/genetics

U2 - 10.1186/s13148-022-01298-4

DO - 10.1186/s13148-022-01298-4

M3 - Article (Academic Journal)

C2 - 35790973

SN - 1868-7075

VL - 14

JO - Clinical Epigenetics

JF - Clinical Epigenetics

IS - 1

M1 - 83

ER -

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

Abstract

Bibliographical note

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