Re-examining social differences in health: Utilising an epigenetic biomarker of smoking

Social differences in health are consistently reported yet it is still not quite clear what the mediating processes are leading to such discrepancies. Health behaviours have been proposed but these may not fully explain all the differences between the most and least disadvantaged groups. Further the relative contribution of health behaviours to social differences in health is not clear because they are subject to measurement error and also interact with other exposures. Further, there have been a number of biological pathways that have been proposed to arbitrate social differences in health but again it is not clear how these may link to upstream pathways such as those involved in inflammation and stress reactivity. In this proposal, I will investigate whether DNA methylation can be used to create a biomarker of smoking by comparing methylation-based estimates with self-reported smoking measures; examine how smoking assessed with a new biomarker and self-report compare in their explanation of social differences in health and; identify whether smoking assessed with DNA methylation is associated with additional biological processes that are socially patterned and how these tobacco-related effects may be controlled for in epigenetic associations.

1. How do self-reported and biomarker measures of smoking compare in their explanation of social differences in health and do more complex smoking biomarkers, such as those able to predict duration or cessation years, account for more of this variation in health?

2. Does AHRR methylation influence cytokine levels and how does this impact associations between inflammatory markers and socioeconomic factors?

3. How do smokers and non-smokers compare in their response to other environmental toxins, such as those related to occupation and how do these interact with smoking in the epigenome?

4. Can smoking effects on AHRR be reproduced in vitro and how are these cells impacted when exposed to toxins other than those found in tobacco?

This research project will make use of a recently created genome-wide DNA methylation resource as part of the UK Household Longitudinal Study (UKHLS), Understanding Society which has been funded primarily by the Economic and Social Research Council (ESRC). Understanding Society is a nationally-representative longitudinal survey and builds on the success of the British Household Panel Survey (BHPS), initiated in 1991, that was heavily used by researchers and generated hundreds of scientific publications. Understanding Society aims to support a wider range of research than BHPS and this DNA methylation resource aims to help in doing so (Buck and McFall, 2011). Methylation was profiled from over 1000 whole blood samples collected during wave 3 and these particular participants had been present at all annual interviews between 1999 and 2011, providing over 10 years of complete lifestyle-related data. Longitudinal studies of this nature can provide understanding of the trajectories of individual life histories and this project will utilise the detailed recorded smoking information available from participant surveys as well as the rich source of information on a number of socioeconomic and health-related variables, namely those relating to socioeconomic classificiations, cardiovascular disease and occupational exposures. The bulk of questionnaire data to be used throughout this project comes from the main survey in wave 3 to enable to closest proximity between DNA methylation profiles and associated socioeconomic factors and health measures. With this said, all analyses and subsequent findings achieved from using this data would greatly benefit from validation in other DNA methylation resources, especially in studies where repeated epigenetic measures are available such as in the 1958 National Child Development Study (NCDS) although how this will relate to adult health in unclear.