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Epigenomics of being bullied: changes in DNA methylation following bullying exposure

dataset
posted on 29.01.2020, 04:25 by Rosa H. Mulder, Esther Walton, Alexander Neumann, Lotte C. Houtepen, Janine F. Felix, Marian J. Bakermans-Kranenburg, Matthew Suderman, Henning Tiemeier, Marinus H. van IJzendoorn, Caroline L. Relton, Charlotte A. M. Cecil

Bullying among children is ubiquitous and associated with pervasive mental health problems. However, little is known about the biological pathways that change after exposure to bullying. Epigenome-wide changes in DNA methylation in peripheral blood were studied from pre- to post measurement of bullying exposure, in a longitudinal study of the population-based Generation R Study and Avon Longitudinal Study of Parents and Children (combined n = 1,352). Linear mixed-model results were meta-analysed to estimate how DNA methylation changed as a function of exposure to bullying. Sensitivity analyses including co-occurring child characteristics and risks were performed, as well as a Gene Ontology analysis. A candidate follow-up was employed for CpG (cytosine-phosphate-guanine) sites annotated to 5-HTT and NR3C1. One site, cg17312179, showed small changes in DNA methylation associated to bullying exposure (b = −2.67e-03, SE = 4.97e-04, p = 7.17e-08). This site is annotated to RAB14, an oncogene related to Golgi apparatus functioning, and its methylation levels decreased for exposed but increased for non-exposed. This result was consistent across sensitivity analyses. Enriched Gene Ontology pathways for differentially methylated sites included cardiac function and neurodevelopmental processes. Top CpG sites tended to have overall low levels of DNA methylation, decreasing in exposed, increasing in non-exposed individuals. There were no gene-wide corrected findings for 5-HTT and NR3C1. This is the first study to identify changes in DNA methylation associated with bullying exposure at the epigenome-wide significance level. Consistent with other population-based studies, we do not find evidence for strong associations between bullying exposure and DNA methylation.

Funding

This work was supported by the Economic and Social Research Council [ES/N000382/1];H2020 Marie Skłodowska-Curie Actions [707404];Horizon 2020 [633595];Horizon 2020 [733206];Koninklijke Nederlandse Akademie van Wetenschappen [-];Nederlandse Organisatie voor Wetenschappelijk Onderzoek [400.17.602];Nederlandse Organisatie voor Wetenschappelijk Onderzoek [024.001.003];Nederlandse Organisatie voor Wetenschappelijk Onderzoek [024.001.003];Nederlandse Organisatie voor Wetenschappelijk Onderzoek [024.001.003];Horizon 2020 Framework Programme () [848158].

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