Abstract
ABSTRACT 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.
Highlights
The social environment is a major contributor to mental health
In the Avon Longitudinal Study of Parents and Children (ALSPAC), bullying exposure was reported by the child at the mean (SD) age of 8.6 (0.2) years, and DNA methylation was measured at 7.5 (0.1) and 17.1 (1.0) years of age (Supplemental Figure 1)
In the main analysis 45.5% of children in the Generation R sample and 39.4% of children in the ALSPAC sample were categorized as exposed to bullying victimization
Summary
The social environment is a major contributor to mental health. Following Olweus’ definition, a person is being bullied ‘when he or she is exposed, repeatedly and over time, to negative actions on the part of one or more other persons’. Such negative actions should be intentional and performed by someone perceived be more powerful than the subject. Bullying exposure (i.e. bullying victimization) has been associated with numerous mental health issues including behavioural problems, depressive symptoms [3,4,5,6] and suicidal ideation [7].
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