Lifecourse social adversity, DNA methylation, and cardiovascular disease risk

Epigenetic modifications such as DNA methylation may represent an important modifiable molecular mechanism through which social adversity early in life contributes to CVD disparities in adulthood. DNA methylation markers may also provide insight into whether modifications due to early life exposures are permanent. However, although DNA methylation is believed to be a dynamic process influenced by changes in the environment, few studies have empirically evaluated the plasticity of methylomic markers to changes in patterns of social adversity over the life course. Furthermore, while studies have hypothesized that these epigenetic modifications increase CVD risk, previous research has not empirically tested whether associations of lifecourse social adversity with CVD risk markers are mediated by methylomic markers. This is an important mechanistic gap in the literature because it limits our understanding of the role DNA methylation plays in social CVD disparities. In response to these critical gaps in the literature, the overall objective of this application is to determine associations of patterns of social adversity over the life course to DNA methylation and cardiometabolic health. We will achieve our objective using 25 years of longitudinal data on 1,200 black and white participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study (18-30 years old at baseline) with gene expression data and whole blood methylation profiling data available at two time points. Specifically, we aim to use epigenome-wide methylation profiling data to identify methylomic markers of social adversity and to test whether associations of lifecourse social adversity with cardiometabolic health are mediated by adversity-associated methylomic markers. A better understanding of the extent to which early life exposures are modifiable is necessary to guide the content and timing of interventions to address social disparities in CVD.