Childhood adversity and DNA methylation in two population-based cohorts

J Maddock,D Kuh,M J Suderman,L D Howe,L C Houtepen,C L Relton,R Hardy,E L Anderson

doi:10.1038/s41398-018-0307-3

Abstract

Childhood adversity affects later health, but the underlying molecular mechanisms are unclear. Although there is some evidence from animal models and case-control studies of a role for DNA methylation, evidence from human population-based studies is limited. In two cohorts (mothers from the Avon Longitudinal Study of Parents and Children, ALSPAC, n = 780 and women from the MRC National Survey of Health and Development, NSHD, n = 552), we assessed the association of seven adverse childhood experiences (ACEs: parental physical illness, parental mental illness, parental death, parental separation, suboptimal maternal bonding, childhood illness and child maltreatment) as well as their combination (ACE score) with genome-wide DNA methylation levels measured using the Illumina Infinium HumanMethylation450 BeadChip in peripheral blood at mean age 47 years (ALSPAC) and in buccal cells at age 53 years (NSHD). CpG sites with a genome-wide false discovery rate (FDR) below 0.05 and differentially methylated regions (DMRs) with one-step Šidák correction p-values below 0.05 in each cohort were examined in the other cohort. No individual CpG sites replicated across cohorts. However, nine DMRs replicated across cohorts respectively associated with the ACE score (one region), parental mental illness (two regions), parental physical illness (three regions) and parental death (three regions). These observations indicate that some adverse childhood experiences, notably those related to parental health, may leave imprints on peripheral DNA methylation that persist to mid-life.

Highlights

Childhood adversity is related to a broad range of negative outcomes across the lifespan including poorer mental and physical health[1,2] as well as lower educational attainment, income and economic participation[3,4]
To demonstrate that the adverse childhood experiences (ACEs) score behaves as expected in relation to mental health, we examined the association of the ACE score with depression, both in the full Avon Longitudinal Study of Parents and Children (ALSPAC) cohort and in the subsample included in our Epigenome-wide association studies (EWAS)
One differentially methylated regions (DMRs) was associated with a measure for cumulative adversity (ACE count score), whereas the other eight regions were associated with specific types of adversity, namely parental mental illness, parental physical illness and parental death

Summary

Introduction

Childhood adversity is related to a broad range of negative outcomes across the lifespan including poorer mental and physical health[1,2] as well as lower educational attainment, income and economic participation[3,4]. Most ACEs had a similar prevalence in the participants without DNA methylation data, and the ACE score demonstrated similar associations with depression in the full cohort of ALSPAC mothers and in the subsample included in our analysis (see Supplementary Tables 2–4).

Results

Conclusion