This innovative multidisciplinary project aims to dissect the epigenetic signatures of stress biology by pioneering novel longitudinal comparisons of monozygotic (identical) twins discordant for psychosocial stress experiences across adolescence. The specific objectives of the study fall into three primary categories:

1. Conducting innovative longitudinal research‌

This biosocial project capitalises upon existing cohort data to explore longitudinal epigenetic signatures of psychosocial stress exposure during adolescence. Optimal technology for epidemiologically-based epigenetic studies and longitudinal samples of 100 stringently characterised discordant MZ twins for exposure to psychosocial stress during adolescence will be used to address these research questions:

How does exposure to psychosocial stress during adolescence impact on the DNA methylome?

Our analysis of repeated measures of DNA methylation before and after the psychosocial stress exposure and comparison with their unexposed genetically identical twin will allow us to establish the longitudinal epigenetic trajectories associated with adolescent psychosocial stress.

What are the epigenetic biomarkers of adolescent exposure to psychosocial stress?

We intend to identify site‐specific/regional differential DNA methylation associated with stress. Also we will explore how the functional organisation of DNA methylation is altered with adolescent psychosocial stress exposure using weighted gene co‐methylation network analysis.

Are psychosocial stress-associated altered epigenetic marks generalizable across tissues or tissue-specific?

A novel comparison of psychosocial stress-associated methylation patterns using buccal and blood DNA will be conducted to ascertain whether the same or different epigenetic stress signatures are found in both tissues.

2. Innovative methodological comparisons and advancement

The proposed study will address social and behavioural epigenetic methodological challenges in two ways:

• Despite the known tissue-specific nature of the DNA methylome, no study to date has studied the impact of psychosocial stress on multiple tissue sources. Our novel parallel DNA methylomic comparison using DNA that captures biological stress responses, will bridge this important knowledge gap and inform future studies.
• The use of longitudinal data in epigenetics remains relatively new. Our multidisciplinary team aims to address this methodological challenge by developing an innovative statistically robust analytical pipeline for longitudinal genome-wide epigenetic data.

3. Building multi-disciplinary capability

Two early career researchers from different disciplines (epigenetics and social epidemiology) have the unique opportunity to lead this biosocial project and share skills. Cross-discipline capability in this exciting field of social and behavioural epigenetics will be further enhanced via a series of multidisciplinary workshops with PhD students.

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The proposed analysis involves the generation and analysis of DNA methylation profiles across childhood and adolescence for monozygotic twins from the MRC‐funded Environmental Risk (E‐Risk) Longitudinal Twin Study, which tracks the development of a birth cohort of 2232 British children. The sample was drawn from a larger birth register of twins born in England and Wales in 1994‐95.

The E‐Risk sample was constructed in 1999‐2000, when 1116 (93% of those eligible) families with same sex 5 year old twins participated in home visit assessments. Families were recruited to represent the UK population of families with newborns in the 1990s, on the basis of residential location throughout England and Wales and mother’s age (older mothers having twins via assisted reproduction were under‐selected, and teenage mothers with twins were over‐selected).

We used this sampling to replace high risk families who were selectively lost to the register through non‐response and to ensure inclusion of sufficient numbers of children growing up in high risk environments. The sample includes 55% monozygotic (identical) and 45% dizygotic (non-identical) twin pairs. Sex is evenly distributed within zygosity (49% male). Follow‐up home visits took place when the children were aged 7 (98% participation), aged 10 (96% participation), aged 12 (96% participation), and most recently, at age 18 (93% participation). Buccal swabs were obtained from the twins at ages 5, 10 and 18, and at age 18 they also provided blood samples. Twins were separately interviewed at age 18 about their exposure to a range of psychosocial stressors during adolescence.