INTERpreting epigenetic signatures in STudies of Early Life Adversity (InterStELA)

Early life adversity can have a significant and lasting effect on social, developmental, and health outcomes; various markers of early life adversity such as low socio-economic position (SEP); parental death, illness or divorce; separation from parents; parental mental health or addiction; lack of warmth and affection of parent-child relationships; residential instability, and physical, emotional and sexual abuse are associated with lower educational attainment, income and economic participation, as well as with adverse health behaviours and poorer mental and physical health outcomes. Reducing or potentially eliminating the harmful effects of early adversity is crucial for combating inequalities.
There is a large body of evidence documenting and describing the long-term consequences of early life adversity, but the pathways and mechanisms through which they occur remain uncertain. In order for early life adversity to influence later outcomes, biological systems must be affected. Epigenetics is a potential molecular mechanism linking early life adversity with later outcomes. DNA methylation is one type of epigenetic change. It is a chemical change to our DNA that influences the extent to which our genes are expressed. DNA methylation can respond to environmental factors in early life, which means it may be very useful to study early life adversity. Animal models have shown links between early life stress and altered methylation patterns, and more recently evidence from human studies has shown that low SEP and abuse are associated with differences in methylation patterns.
The aim of this project is to create a network of researchers working on the relationship between early life adversity and DNA methylation. Bringing together a team of social and biological researchers will enable the researchers to share data and expertise in order to drive the field forwards and speed up progress. The researchers will use existing high-quality data from studies where people have been followed across the life course in order to better understand how early life adversity affects changes in DNA methylation and whether there are other factors that alter these relationships.
In addition to carrying out specific research projects in this area, network members will meet at a series of workshops, in which the results from research will be discussed and future projects will be planned.

The overarching goal of InterSTELA is to further understanding of the relationship between early life adversity and DNA methylation, and to expedite progress and methodological developments in this area. Thus the key groups we anticipate having an impact on are the public, social and health policy makers, and the scientific community.
The research carried out in InterSTELA will be of relevance to the general public, since it aims to further our understanding of the ways in which our lived experiences are embodied. We will ensure that our findings are communicated to the public through public engagement activities, as detailed in the Pathways to Impact section.
Social and health policy makers rely on high quality evidence to inform the design of policies and interventions. Our research will shed light on the potential reversibility of the long-term consequences of early life adversity, and the pathways through which such reversibility may occur. Our findings will thus be useful to inform the design of policies that aim to reduce or alleviate the harms caused by early life adversity, and to predict the potential benefits from such interventions. The inclusion of a wide range of biological and social researchers in the InterSTELA network, many of whom have experience of engaging policy makers and/or in intervention design, will facilitate dissemination to relevant parties.
As detailed in the academic beneficiaries section, our research is of relevance to a wide range of academics. Research findings will be published in high quality peer reviewed journals - both biological and social - and presented at a range of conferences. Methodological innovations will be published in a timely manner, including syntax for widely used statistical software (e.g. Stata or R) and new Stata commands/R packages. Links with other genetic and epigenetic consortia will facilitate our broad academic dissemination strategy, and a network website will advertise the existence of the website and provide a repository for workshop presentations and links to published papers. Another important form of dissemination to the academic community will be training. The School of Social and Community Medicine, University of Bristol hosts a programme of high-quality short courses. We will develop a course focused on early life adversity and epigenetics - this will be delivered internally within the University of Bristol and other partner organisations within the network, as well as being run as a satellite course to at least one major international meeting (funds are requested for this). Through the leadership of InterSTELA by a team of early- and mid-career researchers who are closer to the hands-on conduct of research than our senior colleagues, we aim to promote a strong inter-disciplinary culture and genuine multidisciplinary working (rather than linkage between separate projects run by academics from different disciplines).