Project Summary Cardiovascular diseases (CVD) such as myocardial infarction and stroke are the leading causes of death in the United States (US), and widespread disparities in CVD burden exist across socioeconomic, racial, and ethnic groups. High blood pressure (BP), or hypertension (HTN), is the most prevalent risk factor for CVD. Importantly, higher BP in young adulthood, even within the clinically normal range, tracks with cumulative lifetime exposure to elevated BP levels, leading to earlier development of clinical HTN and significantly greater CVD risk, despite use of optimal antihypertensive therapy later in life. Primordial prevention of BP elevation is therefore needed to reduce HTN-related morbidity. Social determinants of health (SDOH) could contribute to observed disparities in uncontrolled BP and increasing proportions of HTN among US adults. Notably, early life SDOH have been associated with epigenetic changes in DNA methylation (DNAm), potentially accelerating HTN and CVD development, but limited work has considered long-term relationships between early life SDOH, epigenetic mechanisms, and CVD risk factors. Our overarching hypothesis is that early life SDOH are associated with young adult BP levels, and that DNAm statistically mediates these associations. To examine this hypothesis, we will pursue the following Specific Aims: 1) investigate early life SDOH and young adult BP associations, 2) investigate temporal associations between DNAm and young adult BP, evaluating DNAm as a mediator of SDOH-BP associations, and 3) replication to examine the durability of these associations. We will primarily utilize the Future of Families and Child Wellbeing Study (FFCWS), a diverse prospective cohort study collecting phenotype, genotype, epigenetic, and parental data in children from birth to young adulthood. In Aim 1, multi-trajectory modeling and latent class analysis will assess SDOH trajectories and cumulative exposures. Aim 2 will involve epigenome-wide association and mixed-effect models to examine repeated longitudinal measures of SDOH and DNAm. Standard and high-dimensional mediation analyses can quantify DNAm effects within SDOH-BP associations. Aim 3 replication of FFCWS association and mediation analyses will be performed in the diverse community-based CARDIA cohort, which has collected extensive SDOH, phenotype, genotype, and epigenetic data in participants from young adulthood through middle age. This work will provide longitudinal insight into the complex interplay between SDOH, epigenetics, and BP, deepening our understanding of primordial risk factor prevention and tailored interventions to prevent HTN. If awarded, this fellowship will allow me to contribute novel research to the SDOH and CVD fields, gain competency in the development and application of biomedical informatics and analytical methods, and improve my writing and presentation skills, while learning from a sponsor team with extensive subject matter and mentorship ex...