Childhood adversity and DNA methylation in two population-based cohorts

Area of Science:

• Epigenetics
• Developmental Origins of Health and Disease (DOHaD)
• Molecular Epidemiology

Background:

• Childhood adversity impacts adult health, but molecular pathways remain unclear.
• DNA methylation is a potential mechanism, yet human population data is scarce.
• Previous evidence stems mainly from animal models and case-control studies.

Purpose of the Study:

• To investigate the association between Adverse Childhood Experiences (ACEs) and genome-wide DNA methylation in human population cohorts.
• To identify specific differentially methylated regions (DMRs) that replicate across independent cohorts.

Main Methods:

• Utilized two large UK cohorts (ALSPAC and NSHD) with genome-wide DNA methylation data (Illumina 450k array).
• Assessed seven types of ACEs and an overall ACE score.
• Analyzed peripheral blood (ALSPAC) and buccal cells (NSHD) methylation at mid-life.

Main Results:

• No individual CpG sites associated with ACEs replicated across cohorts.
• Nine DMRs replicated across cohorts, linked to ACE score, parental mental illness, parental physical illness, and parental death.
• Specific associations were strongest for parental health-related ACEs.

Conclusions:

• Adverse Childhood Experiences, especially those concerning parental health, can leave persistent epigenetic imprints.
• These DNA methylation changes are detectable in mid-life.
• Findings support a molecular link between early-life adversity and later-life health outcomes.