Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation

Anna Kotsakis Ruehlmann; Sara Sammallahti; Andrea P. Cortés Hidalgo; Kelly M. Bakulski; Elisabeth B. Binder; Megan Loraine Campbell; Doretta Caramaschi; Charlotte A.M. Cecil; Elena Colicino; Cristiana Cruceanu; Darina Czamara; Linda Dieckmann; John Dou; Janine F. Felix; Josef Frank; Siri E. Håberg; Gunda Herberth; Thanh T. Hoang; Lotte C. Houtepen; Anke Hüls; Nastassja Koen; Stephanie J. London; Maria C. Magnus; Giulia Mancano; Rosa H. Mulder; Christian M. Page; Katri Räikkönen; Stefan Röder; Rebecca J. Schmidt; Tabea S. Send; Gemma Sharp; Dan J. Stein; Fabian Streit; Johanna Tuhkanen; Stephanie H. Witt; Heather J. Zar; Ana C. Zenclussen; Yining Zhang; Lea Zillich; Rosalind Wright; Jari Lahti; Kelly J. Brunst

doi:10.1038/s41380-023-02010-5

Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation

Anna Kotsakis Ruehlmann, Sara Sammallahti, Andrea P. Cortés Hidalgo, Kelly M. Bakulski, Elisabeth B. Binder, Megan Loraine Campbell, Doretta Caramaschi, Charlotte A.M. Cecil, Elena Colicino, Cristiana Cruceanu, Darina Czamara, Linda Dieckmann, John Dou, Janine F. Felix, Josef Frank, Siri E. Håberg, Gunda Herberth, Thanh T. Hoang, Lotte C. Houtepen, Anke HülsNastassja Koen, Stephanie J. London, Maria C. Magnus, Giulia Mancano, Rosa H. Mulder, Christian M. Page, Katri Räikkönen, Stefan Röder, Rebecca J. Schmidt, Tabea S. Send, Gemma Sharp, Dan J. Stein, Fabian Streit, Johanna Tuhkanen, Stephanie H. Witt, Heather J. Zar, Ana C. Zenclussen, Yining Zhang, Lea Zillich, Rosalind Wright, Jari Lahti, Kelly J. Brunst

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Abstract

Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N = 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1 and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.

Original language	English
Pages (from-to)	5090-5100
Number of pages	11
Journal	Molecular Psychiatry
Volume	28
Issue number	12
DOIs	https://doi.org/10.1038/s41380-023-02010-5
State	Published - Dec 2023

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Kotsakis Ruehlmann, A., Sammallahti, S., Cortés Hidalgo, A. P., Bakulski, K. M., Binder, E. B., Campbell, M. L., Caramaschi, D., Cecil, C. A. M., Colicino, E., Cruceanu, C., Czamara, D., Dieckmann, L., Dou, J., Felix, J. F., Frank, J., Håberg, S. E., Herberth, G., Hoang, T. T., Houtepen, L. C., ... Brunst, K. J. (2023). Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation. Molecular Psychiatry, 28(12), 5090-5100. https://doi.org/10.1038/s41380-023-02010-5

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title = "Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation",

abstract = "Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N = 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1 and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.",

author = "{Kotsakis Ruehlmann}, Anna and Sara Sammallahti and {Cort{\'e}s Hidalgo}, {Andrea P.} and Bakulski, {Kelly M.} and Binder, {Elisabeth B.} and Campbell, {Megan Loraine} and Doretta Caramaschi and Cecil, {Charlotte A.M.} and Elena Colicino and Cristiana Cruceanu and Darina Czamara and Linda Dieckmann and John Dou and Felix, {Janine F.} and Josef Frank and H{\aa}berg, {Siri E.} and Gunda Herberth and Hoang, {Thanh T.} and Houtepen, {Lotte C.} and Anke H{\"u}ls and Nastassja Koen and London, {Stephanie J.} and Magnus, {Maria C.} and Giulia Mancano and Mulder, {Rosa H.} and Page, {Christian M.} and Katri R{\"a}ikk{\"o}nen and Stefan R{\"o}der and Schmidt, {Rebecca J.} and Send, {Tabea S.} and Gemma Sharp and Stein, {Dan J.} and Fabian Streit and Johanna Tuhkanen and Witt, {Stephanie H.} and Zar, {Heather J.} and Zenclussen, {Ana C.} and Yining Zhang and Lea Zillich and Rosalind Wright and Jari Lahti and Brunst, {Kelly J.}",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature Limited 2023.",

year = "2023",

month = dec,

doi = "10.1038/s41380-023-02010-5",

language = "English",

volume = "28",

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journal = "Molecular Psychiatry",

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Kotsakis Ruehlmann, A, Sammallahti, S, Cortés Hidalgo, AP, Bakulski, KM, Binder, EB, Campbell, ML, Caramaschi, D, Cecil, CAM, Colicino, E, Cruceanu, C, Czamara, D, Dieckmann, L, Dou, J, Felix, JF, Frank, J, Håberg, SE, Herberth, G, Hoang, TT, Houtepen, LC, Hüls, A, Koen, N, London, SJ, Magnus, MC, Mancano, G, Mulder, RH, Page, CM, Räikkönen, K, Röder, S, Schmidt, RJ, Send, TS, Sharp, G, Stein, DJ, Streit, F, Tuhkanen, J, Witt, SH, Zar, HJ, Zenclussen, AC, Zhang, Y, Zillich, L, Wright, R, Lahti, J & Brunst, KJ 2023, 'Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation', Molecular Psychiatry, vol. 28, no. 12, pp. 5090-5100. https://doi.org/10.1038/s41380-023-02010-5

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AU - Cortés Hidalgo, Andrea P.

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AU - Binder, Elisabeth B.

AU - Campbell, Megan Loraine

AU - Caramaschi, Doretta

AU - Cecil, Charlotte A.M.

AU - Colicino, Elena

AU - Cruceanu, Cristiana

AU - Czamara, Darina

AU - Dieckmann, Linda

AU - Dou, John

AU - Felix, Janine F.

AU - Frank, Josef

AU - Håberg, Siri E.

AU - Herberth, Gunda

AU - Hoang, Thanh T.

AU - Houtepen, Lotte C.

AU - Hüls, Anke

AU - Koen, Nastassja

AU - London, Stephanie J.

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AU - Page, Christian M.

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AU - Schmidt, Rebecca J.

AU - Send, Tabea S.

AU - Sharp, Gemma

AU - Stein, Dan J.

AU - Streit, Fabian

AU - Tuhkanen, Johanna

AU - Witt, Stephanie H.

AU - Zar, Heather J.

AU - Zenclussen, Ana C.

AU - Zhang, Yining

AU - Zillich, Lea

AU - Wright, Rosalind

AU - Lahti, Jari

AU - Brunst, Kelly J.

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AB - Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N = 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1 and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.

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SP - 5090

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JO - Molecular Psychiatry

JF - Molecular Psychiatry

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ER -

Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation

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