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Transl Psychiatry. 2018 Oct 2;8(1):194. doi: 10.1038/s41398-018-0252-1.

Exposure to childhood abuse is associated with human sperm DNA methylation.

Author information

1
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. aroberts@hsph.harvard.edu.
2
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, and BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.
3
Beedie School of Business, Simon Fraser University, Burnaby, BC, Canada.
4
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
5
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
6
Division of Adolescent and Young Adult Medicine, Boston Children's Hospital, Boston, MA, USA.
7
Department of Urology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
8
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
9
Laboratory of Environmental Precision Biosciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
10
Human Early Learning Partnership, School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.

Abstract

Offspring of persons exposed to childhood abuse are at higher risk of neurodevelopmental and physical health disparities across the life course. Animal experiments have indicated that paternal environmental stressors can affect sperm DNA methylation and gene expression in an offspring. Childhood abuse has been associated with epigenetic marks in human blood, saliva, and brain tissue, with statistically significant methylation differences ranging widely. However, no studies have examined the association of childhood abuse with DNA methylation in gametes. We examined the association of childhood abuse with DNA methylation in human sperm. Combined physical, emotional, and sexual abuse in childhood was characterized as none, medium, or high. DNA methylation was assayed in 46 sperm samples from 34 men in a longitudinal non-clinical cohort using HumanMethylation450 BeadChips. We performed principal component analysis and examined the correlation of principal components with abuse exposure. Childhood abuse was associated with a component that captured 6.2% of total variance in DNA methylation (p < 0.05). Next, we investigated the regions differentially methylated by abuse exposure. We identified 12 DNA regions differentially methylated by childhood abuse, containing 64 probes and including sites on genes associated with neuronal function (MAPT, CLU), fat cell regulation (PRDM16), and immune function (SDK1). We examined adulthood health behaviors, mental health, and trauma exposure as potential mediators of an association between abuse and DNAm, and found that mental health and trauma exposure partly mediated the association. Finally, we constructed a parsimonious epigenetic marker for childhood abuse using a machine learning approach, which identified three probes that predicted high vs. no childhood abuse in 71% of participants. Our results suggested that childhood abuse is associated with sperm DNA methylation, which may have implications for offspring development. Larger samples are needed to identify with greater confidence specific genomic regions differentially methylated by childhood abuse.

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