Epigenetic Epidemiology: Caroline Relton
This programme aims to identify causes and consequences of variation in DNA methylation using population-based studies. The programme aims to integrate multiple sources of omics data together with epigenetic information, and combine these with the development and application of causal analysis methods. It seeks to identify novel biomarkers and develop predictive tools that index exposures and predict disease onset and progression, with the aim of enhancing disease prevention.
We utilize biological samples from a variety of established cohort resources and are closely allied to both boinformatic and statistical themes within the Unit. The work is supported by an extensive network of external collaborators and industrial partners and has been enhanced through securing additional funding for allied project and programmatic research in epigenetic epidemiology.
Aims and Objectives
- Identify genetic and environmental determinants of epigenetic variation, including a genome-wide association study of DNA methylation;
- Demonstrate the value of epigenetic signatures as indicators of exposures acting at different stages of the life course;
- Investigate the relationship between epigenetic variation and phenotype (e.g. cardiometabolic, musculoskeletal and neurodevelopmental traits) in ALSPAC and other complementary cohorts;
- Develop and apply statistical approaches to analyse changes in epigenetic patterns over the lifecourse and their relation to health and development;
- Develop and apply novel methodologies to strengthen causal inference in the context of epigenetics;
- Undertake functional characterization of epidemiological associations observed on the exposure/epigenome/phenotype pathway
Current Postdoctoral Research Associates and Fellows
Dr Hannah Elliott 2009-
Dr Gemma Sharp 2013-
Dr Matthew Suderman 2013-
Dr Doretta Caramaschi 2013-
Dr Philip Haycock 2013-
Dr Josine Min 2014-
Dr Kim Burrows 2015-
Dr Rebecca Richmond 2015-
Dr Kaitlin Wade 2015-2016
Dr Nabila Kazmi 2014-
Dr Santi Rodriguez 2015-
Dr Tom Richardson 2016-
Dr Paul Yousefi 2016-
Dr Leanne Kupers 2016-
2012- Mary Ward, PhD “The role of the epigenome in mediating the causes and consequences of physical activity levels”
2013- Jessica Timms, PhD “Influence of early environmental exposures on epigenetic markers of leukaemia in infants” (University of Newcastle)
2013- Ryan Arathimos, PhD “Molecular epidemiology of asthma patterns across childhood”
2014- James Jungius, PhD “Prenatal exposures, offspring health and mediation by DNA methylation”
2014- Aayah Nounu, PhD “Using epigenetics and metabolomics to identify mechanisms of action of aspirin in colorectal cancer”
2015- Diana Juvinao-Quintero, PhD “Epigenetic variation and type 2 diabetes related traits: investigating causal relationships”
2015- James Yarmolinsky, PhD “Causal effects of BMI on cancer risk”
2015- Katie Berryman, PhD “An epigenome-wide study of eczema”
2015- Tamsin Sharp, PhD “Neurodevelopmental consequences of prenatal alcohol exposure: a population-based MRI study”
2015- Ryan Langdon, PhD “The use of the human DNA methylome to establish cancer risk biomarkers in high risk HPV-infected individuals”
Developing population-based approaches in the field of epigenetics research
The field of epigenetics has escalated very rapidly in recent years. We have applied population-based approaches (epidemiological methods) to aid the understanding of the determinants and consequences of epigenetic variation in health and development.
Exploring the genetics of epigenetics
The role of common genetic variation in determining DNA methylation is an area of biology that remains largely unexplored. Having established a large population-based data set of both mothers and children at multiple time points across the life course we undertook a large scale genome-wide association study of DNA methylation. This demonstrates widespread meQTLs and provides insight into their stability over time as well as the contribution they make to common complex diseases. This work is being extended through the establishment of the Genetics of DNA Methylation Consortium (GoDMC)
Pioneering causal analysis methods in epigenetic epidemiology
Central to the emergence of epigenetic epidemiology as a discipline has been the development and application of methods to strengthen causal inference. We have extended the conventional method of Mendelian randomization to facilitate its application in epigenetic studies. This and other causal analysis tools are becoming increasingly incorporated into population-based epigenetic studies.
Identifying early life influences on child and adult health and development
The developmental origins of health and disease is now a well-accepted paradigm whereby early life influences can shape the risk of disease in later life. Epigenetic mechanisms are proposed to play an important role in mediating these effects. We have undertaken several large scale studies of maternal prenatal and early life influences on the offspring epigenome. Evidence supports a role for epigenetic mechanisms in some domains.
Identifying biomarkers of cancer risk
A long standing interest in the role of one carbon metabolism in disease aetiology risk has highlighted the potential for one carbon intermediates to act as early biomarkers of cancer. This links logically with the role of one carbon metabolism in methyl group donation and this work is expanding to include analysis of epigenetic variation as a biomarker (or mechanistic pathway) in several cancer types.