Association of DNA Methylation and Stress in Immigrants - PROJECT SUMMARY Immigrants experience significant health disparities which are exacerbated by a heavy stress burden which in turn affects the epigenetic profiles of the immune system leading to chronic diseases. Cumulative stress burden for immigrant’s ranges from immigration-related stressors to unique psychosocial, environmental, and everyday challenges, all of which contribute to negative psychological and biological impacts on their health over the life- course. Although social and environmental conditions have been established as key factors driving disparities in health outcomes, the effects of stress and epigenetic change among immigrants remains poorly understood, impeding the development of novel and robust intervention approaches aimed at reducing health disparities. Epigenetic changes can act as surrogate markers for stress effect. However, very few studies have examined epigenetic marks associated with stress among African immigrants. Ethiopians form one of the largest groups of African immigrants in the US, yet this is the first study of this kind among Ethiopian American immigrants (EAIs). The objective of this proposal is to quantify cumulative stress burden and determine DNA methylation associated with stress among EAIs. We hypothesize that the DNA methylation profile in EAIs is associated with cumulative stress. To address cultural differences and experiences and for a wider translation to the community, our bilingual and bicultural multidisciplinary research team will work with relevant scientific partners connected to and/or part of EAI communities in Cincinnati and Columbus OH to achieve two Specific Aims: Aim 1) Measure cumulative stress burden and identify and define stress burden profiles among EAIs. Aim 2) Determine the association between cumulative stress and DNA methylation. Our proposed study, involving a comprehensive set of cumulative stress measures and genome- wide DNA methylation among an immigrant population, is the first study among Ethiopian American immigrants. The study will provide new insights to address health disparities among growing immigrant populations in the US informing novel and robust intervention approaches to reduce chronic illness and associated sequelae for vulnerable populations. Our long-term goal is to better understand how changes in psychological, social, environmental, and acculturative stressors affect the risk for chronic diseases through epigenomic mechanisms.