Social Circumstances and Epigenomics Promoting Health in Three Countries

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"This project proposes an integrated set of aims and analyses of existing social and epigenetic data
from three national studies of aging in the family of Health and Retirement studies (the US Health
and Retirement Study (HRS), the Northern Ireland Cohort for the Longitudinal Study of Ageing
(NICOLA), and the Irish Longitudinal Study of Aging (TILDA)); assays of existing samples to produce
longitudinal epigenetic data for the three countries are also proposed. Comparative analyses based
on these data will address central questions about how life circumstances in both childhood and
adulthood affect epigenetic change and how different historical and life-course exposures in these
countries may result in differential patterns of associations. The project will also examine how
epigenetic changes in turn are associated with health after age 50. The proposal is submitted in
response to the US-Ireland Research and Development Partnership, a unique research initiative
involving funding agencies from the United States (US), the Republic of Ireland (RofI), and Northern
Ireland (NI). Proposals are submitted to each of the three countries with funding requested for each
country's participation from their respective grant agency (e.g., US NIH); grant review is done only by
NIH for all three projects based on this proposal. The project will examine the links between lifetime
social, economic, psychological, environmental and behavioral circumstances, and epigenetic
markers related to aging and health, and subsequent health. Epigenetic modification is one of the
“hallmarks” of aging, i.e. an underlying physiological change that can speedup or delay aging-related
health outcomes. Faster aging is characteristic of people in adverse social circumstances and
epigenetic change, particularly DNA methylation (DNAm), appears to be especially influenced by
adverse social circumstances, both at early ages and at later ages. This project will be unique in
evaluating how a variety of social circumstances, i.e. low levels of education and income, minority
group membership, adverse childhood experiences, adult traumas, risky health behaviors,
psychological states, and chronic stress, are associated with epigenetic markers in three different
countries, with somewhat different historical, social and behavioral characteristics which are
operating in different health policy regimes – allowing for both replication where effects are
hypothesized to be similar and differentiation where they are hypothesized to differ (e.g., where risk
characteristics are differentially patterned by SES). The applicants are uniquely placed with their
resources to explore how socioeconomic experiences across the life course alter epigenetic profiles
to influence health outcomes such as biological dysregulation, frailty, disability, chronic disease, and
premature mortality. The three data sets have been harmonized for information collection from the
beginning of the studies and were designed to encourage comparative analysis. They have been
harmonized in the survey information and the development of the epigenetic data in the three
countries. Each country has strong independent research teams who bring unique expertise and
resources and a history of collaboration to this collaborative proposal."