Environmental and Social Exposure Factors, Epigenetics, and Metabolic Health in Puerto Rican Adults - Type 2 Diabetes (T2D) is one of the fastest-growing chronic diseases globally and contributes substantially to disability, reduced workforce productivity, premature mortality, and rising healthcare costs. In the United States, certain population groups, including individuals of Puerto Rican heritage, experience significantly higher rates of T2D compared to national averages. While behavioral risk factors such as diet and physical activity have been proposed as contributors to this elevated burden, contextual environmental and psychosocial conditions may play an equally important and understudied role. To address this gap, we leverage two complementary cohorts: the Boston Puerto Rican Health Study (BPRHS) and the Puerto Rico Observational Study of Psychosocial, Environmental, and Chronic Disease Trends (PROSPECT). These cohorts represent Puerto Rican adults living in two distinct sociogeographic environments—the Northeast U.S. and the island of Puerto Rico—offering a unique opportunity to examine the biological impact of differing external exposures on metabolic health. Emerging research suggests that chronic external exposures and protective social conditions may influence biological systems via epigenomic modifications such as DNA methylation. Yet, the mechanisms linking these exposures to biological markers of T2D remain unclear. This project proposes to investigate how differential exposure to psychosocial and environmental conditions influences epigenetic patterns related to T2D risk. Our central hypotheses are: (1) Puerto Rican adults residing in Boston are more likely to encounter higher-burden environmental and social contexts, and fewer protective conditions, compared to those residing in Puerto Rico; and (2) these exposure differences contribute to distinct DNA methylation profiles associated with T2D susceptibility. We will address these hypotheses through Specific Aims: - Aim 1: Determine genome-wide DNA methylation differences associated with metabolic pathways relevant to T2D in Puerto Rican adults living in Boston versus those living in Puerto Rico, using 700 blood samples per cohort. - Aim 2: Characterize associations between specific external exposures (e.g., early life adversity, neighborhood conditions, social connections) and protective factors with DNA methylation and T2D-relevant metabolic indicators. Discovery will occur in BPRHS, with replication in PROSPECT. - Aim 3: Assess the relationship between cumulative psychosocial and environmental exposures and biological age acceleration, using established epigenetic aging clocks. By defining the biological mechanisms that link exposure to metabolic risk, this study will inform the development of actionable prevention strategies and improve understanding of chronic disease vulnerability across distinct U.S. communities. The project will expand upon established infrastructure and long-standing collaborative expertise to generate impactful, translational insights into the biology of T2D.
