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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.

SUBMITTER: Kotsakis Ruehlmann A 

PROVIDER: S-EPMC12486153 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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

Kotsakis Ruehlmann Anna A   Sammallahti Sara S   Cortés Hidalgo Andrea P AP   Bakulski Kelly M KM   Binder Elisabeth B EB   Campbell Megan Loraine ML   Caramaschi Doretta D   Cecil Charlotte A M CAM   Colicino Elena E   Cruceanu Cristiana C   Czamara Darina D   Dieckmann Linda L   Dou John J   Felix Janine F JF   Frank Josef J   Håberg Siri E SE   Herberth Gunda G   Hoang Thanh T TT   Houtepen Lotte C LC   Hüls Anke A   Koen Nastassja N   London Stephanie J SJ   Magnus Maria C MC   Mancano Giulia G   Mulder Rosa H RH   Page Christian M CM   Räikkönen Katri K   Röder Stefan S   Schmidt Rebecca J RJ   Send Tabea S TS   Sharp Gemma G   Stein Dan J DJ   Streit Fabian F   Tuhkanen Johanna J   Witt Stephanie H SH   Zar Heather J HJ   Zenclussen Ana C AC   Zhang Yining Y   Zillich Lea L   Wright Rosalind R   Lahti Jari J   Brunst Kelly J KJ  

Molecular psychiatry 20230310 12


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 bloo  ...[more]

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2022-04-22 | GSE201016 | GEO