Childhood-onset lupus is a disease that increases the risk for organ damage and death compared to adult-onset disease. Studies have suggested that genetics contributes to both risk of developing lupus as well as specific features of lupus such as kidney disease. In addition to the contribution by genetics, epigenetics and environmental influences have also been shown to contribute to lupus risk in adult patients. Epigenetics are chemical changes to genetic structure that effectively turns genes “on” or “off”, but do not change genetic sequence. While epigenetic changes have been associated with increased risk of developing lupus in adults, this association has not been extensively studied in children with lupus. Our project aims to collect blood samples from children and teens enrolled in the CARRA Lupus registry to characterize epigenetic changes in youth with lupus. We will explore the relationship between epigenetic changes and disease manifestations, course and severity. Our novel study will provide much needed insight to the role of epigenetics and differences in symptoms and severity in this vulnerable patient population, with the goal of providing insight into what causes increased lupus severity in some patients while sparing others, and lay the foundation for identifying future therapeutic targets.