TY - JOUR
T1 - Childhood adversity correlates with stable changes in DNA methylation trajectories in children and converges with epigenetic signatures of prenatal stress
AU - Martins, Jade
AU - Czamara, Darina
AU - Sauer, Susann
AU - Rex-Haffner, Monika
AU - Dittrich, Katja
AU - Dörr, Peggy
AU - de Punder, Karin
AU - Overfeld, Judith
AU - Knop, Andrea
AU - Dammering, Felix
AU - Entringer, Sonja
AU - Winter, Sibylle M.
AU - Buss, Claudia
AU - Heim, Christine
AU - Binder, Elisabeth B.
N1 - Funding Information:
This study was funded by the German Federal Ministry of Education and Research (BMBF) 01KR1301-A (to CH) and 01KR1301-B and 01GL1743-C (to EBB). The research was conducted at Charité − Universitätsmedizin Berlin, Berlin, Germany, and the Max Planck Institute of Psychiatry, Munich, Germany.
Funding Information:
This study was funded by the German Federal Ministry of Education and Research (BMBF) 01KR1301-A (to CH) and 01KR1301-B and 01GL1743-C (to EBB). The research was conducted at Charité − Universitätsmedizin Berlin, Berlin, Germany , and the Max Planck Institute of Psychiatry, Munich, Germany .
Publisher Copyright:
© 2021 The Authors
PY - 2021/11
Y1 - 2021/11
N2 - Childhood maltreatment (CM) is an established major risk factor for a number of negative health outcomes later in life. While epigenetic mechanisms, such as DNA methylation (DNAm), have been proposed as a means of embedding this environmental risk factor, little is known about its timing and trajectory, especially in very young children. It is also not clear whether additional environmental adversities, often experienced by these children, converge on similar DNAm changes. Here, we calculated a cumulative adversity score, which additionally to CM includes socioeconomic status (SES), other life events, parental psychopathology and epigenetic biomarkers of prenatal smoking and alcohol consumption. We investigated the effects of CM alone as well as the adversity score on longitudinal DNAm trajectories in the Berlin Longitudinal Child Study. This is a cohort of 173 children aged 3–5 years at baseline of whom 86 were exposed to CM. These children were followed-up for 2 years with extensive psychometric and biological assessments as well as saliva collection at 5 time points providing genome-wide DNAm levels. Overall, only a few DNAm patterns were stable over this timeframe, but less than 10 DNAm regions showed significant changes. At baseline, neither CM nor the adversity score associated with DNAm changes. However, in 6 differentially methylated regions (DMRs), CM and the adversity score significantly moderated DNAm trajectories over time. A number of these DMRs have previously been associated with adverse prenatal exposures. In our study, children exposed to CM also presented with epigenetic signatures indicative of increased prenatal exposure to tobacco and alcohol, as compared to non-CM exposed children. These epigenetic signatures of prenatal exposure strongly correlate with DNAm regions associated with CM and the adversity score. Finally, weighted correlation network analysis revealed a module of CpGs exclusively associated with CM. While our study identifies DNAm loci specifically associated with CM, especially within long non-coding RNAs, the majority of associations were found with the adversity score with convergent association with indicators of adverse prenatal exposures. This study highlights the importance of mapping not only of the epigenome but also the exposome and extending the observational timeframe to well before birth.
AB - Childhood maltreatment (CM) is an established major risk factor for a number of negative health outcomes later in life. While epigenetic mechanisms, such as DNA methylation (DNAm), have been proposed as a means of embedding this environmental risk factor, little is known about its timing and trajectory, especially in very young children. It is also not clear whether additional environmental adversities, often experienced by these children, converge on similar DNAm changes. Here, we calculated a cumulative adversity score, which additionally to CM includes socioeconomic status (SES), other life events, parental psychopathology and epigenetic biomarkers of prenatal smoking and alcohol consumption. We investigated the effects of CM alone as well as the adversity score on longitudinal DNAm trajectories in the Berlin Longitudinal Child Study. This is a cohort of 173 children aged 3–5 years at baseline of whom 86 were exposed to CM. These children were followed-up for 2 years with extensive psychometric and biological assessments as well as saliva collection at 5 time points providing genome-wide DNAm levels. Overall, only a few DNAm patterns were stable over this timeframe, but less than 10 DNAm regions showed significant changes. At baseline, neither CM nor the adversity score associated with DNAm changes. However, in 6 differentially methylated regions (DMRs), CM and the adversity score significantly moderated DNAm trajectories over time. A number of these DMRs have previously been associated with adverse prenatal exposures. In our study, children exposed to CM also presented with epigenetic signatures indicative of increased prenatal exposure to tobacco and alcohol, as compared to non-CM exposed children. These epigenetic signatures of prenatal exposure strongly correlate with DNAm regions associated with CM and the adversity score. Finally, weighted correlation network analysis revealed a module of CpGs exclusively associated with CM. While our study identifies DNAm loci specifically associated with CM, especially within long non-coding RNAs, the majority of associations were found with the adversity score with convergent association with indicators of adverse prenatal exposures. This study highlights the importance of mapping not only of the epigenome but also the exposome and extending the observational timeframe to well before birth.
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U2 - 10.1016/j.ynstr.2021.100336
DO - 10.1016/j.ynstr.2021.100336
M3 - Article
C2 - 34095363
AN - SCOPUS:85106953491
SN - 2352-2895
VL - 15
JO - Neurobiology of Stress
JF - Neurobiology of Stress
M1 - 100336
ER -