Overview

A project looking at existing epigenetic data using specialist tools of bioinformatics and statistics to analyse and interpret the life course data on the complex, bidirectional relationship between epigenetic, phenotypic and sociocultural domains. Implicit in the project is building capacity and achieving effective communication across multiple disciplines to incorporate epigenetic research into existing and future activities.

Early life influences and epigenetic mechanisms

Early life influences shape our development, health and behavioural outcomes across the life course. Epigenetic mechanisms are increasingly implicated in these complex interactions and provide a key to understanding: 

• What aspects of our environment impact upon gene regulation
• How our environment and way of living become embodied in human biology, over what timeframe and with what degree of persistence
• How social and biological inequality may influence development and health.

This project builds upon a substantial foundation of epigenetic research in richly characterised longitudinal cohort studies to explore these concepts of environment, embodiment and equality. 

Longitudinal cohort studies

We will utilise the Avon Longitudinal Study of Parents and Children which currently has the most extensive collection of longitudinal epigenetic data of any birth cohort study in the world, as a platform to address these concepts. Through collaboration with seven other cohorts, we will extend our investigations across the entire life course to understand how different social and environmental experiences in early life operate to influence epigenetic signatures and downstream outcomes. We will extend these analyses by implementing causal analysis methods, including novel applications of Mendelian randomization, to strengthen causal inference in the associations we observe. Further, we will apply social constructs / theories to elaborate these interpretations.

Complex data analysis through bioinformatics and statistics

Analysis of the role of epigenetic processes in linking the environment with development and health across the life course requires the capacity to generate, analyse and interpret complex data. The high dimensional, dynamic characteristics of epigenetic data require advanced competencies in bioinformatics and statistical methods. We have invested considerable effort in generating epigenetic data, developing and refining informatics and statistical skills over recent years and through this project propose to apply them to the questions outlined above.

Interdisciplinary collaboration of social and biological scientists

The proposed work will extend current research activities, drawing together skills of social and biological scientists to apply recently developed methodologies to unresolved issues at the interface of epigenetics and social science. A major component of project activities will be the promotion of inter-disciplinary collaboration, training opportunities and widespread dissemination of both methods and scientific outputs. We will draw upon the expertise of our co-investigator team in:

• bioinformatics
• computational science
• econometrics
• education
• epigenetics
• life course epidemiology
• psychology
• quantitative genetics
• social science
• statistics.

Resources

The vast majority of proposed analysis involves secondary analysis of existing data, rather than the design, collection and analysis of new data. A small amount of new data generation is proposed.

DNA methylation data will be analysed from 8 longitudinal cohort studies:

• Avon Longitudinal Study of Parents and Children 
• Born in Bradford (BiB) 
• Southall and Brent Revisited Study (SABRE)
• National Survey of Health and Development (NSHD)
  
• 1921 Lothian Birth Cohort 
• 1936 Lothian Birth Cohort 
• Brisbane Systems Genetics Study (BSGS)
• Twins UK 

Genetic data will be sought from a further 8 longitudinal cohort studies to implement Mendelian randomization analyses (using genotype as a proxy for a specific exposure or for DNA methylation levels):

• 1958 Birth Cohort (1958BC) 
• British Women’s Heart and Health Study (BWHHS) 
• Caerphilly Prospective Study (CAPS) 
• English Longitudinal Study of Ageing (ELSA) 
• UK Biobank 
• Twins Early Development Study (TEDS) 
• PROstate TEsting for Cancer and Treatment Study (PROTECT) 
• UK Household Longitudinal Study (Understanding Society)