Abstract
This study reveals the influence of child maltreatment on DNA methylation across the genome and provides the first evidence that a psychosocial intervention program, the Nurse Family Partnership (NFP), which targets mothers at risk for abusive parenting, associates with variation in the DNA methylome in adult offspring. The 188 participants were born to women randomly assigned to control (n = 99) or nurse-visited intervention groups (n = 89) and provided blood samples and a diagnostic interview at age 27 years. Interindividual variation in the blood DNA methylome was described using principal components (PC) scores derived from principal component analysis and showed that the NFP program (PC10: p = 0.029) and a history of abuse/neglect (PC1: p = 0.029, PC2: p = 0.009) significantly associated with DNA methylome variation at 27 years of age independent of gender, ancestry, cellular heterogeneity, and a polygenic risk index for major psychiatric disorders. The magnitude of the association between child maltreatment and DNA methylation was reduced when accounting for lifestyle factors, including smoking. These findings reflect the sustained impact of both childhood adversity as well as intervention programs that target such adversity on the epigenome but highlight the need for prospective longitudinal studies of DNA methylome variation in the context of early intervention programs.
Highlights
Childhood adversity increases the risk for most forms of non-communicable chronic diseases[1]
We focused our analysis on autosomal CpGs showing interindividual variation in DNA methylation, denoted as variably methylated CpGs. vCpGs were subjected to principal component analysis (PCA) within Array Studio (OmicSoft)
child abuse/ neglect (CAN) was significantly associated with Principal component 1 (PC1) and PC2, which together accounted for ~14% of the interindividual variation in DNA methylation across the human genome in adulthood
Summary
Childhood adversity increases the risk for most forms of non-communicable chronic diseases[1]. Childhood adversity associates with chemically stable, epigenetic modifications, such as DNA methylation[2,3,4], which may maintain the environmental effect on genomic function and health[3]. One study to date has provided some evidence that a psychosocial intervention may moderate the effects of parental depression on features of the DNA methylome such as the epigenetic age[9,10]. Data from programs of early intervention, with establishing clinical efficacy, are lacking. Such evidence is required to evaluate the clinical utility of the DNA methylome for personalized approaches in the fields of perinatal psychiatry and child/ adolescent mental health.
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