The Impact of Wildfire Exposure on the Human Methylome and Health - PROJECT SUMMARY/ABSTRACT Wildfires are a common occurrence in the western United States, increasing in both intensity and number of acres burned over the past few decades as a result of climate change. The effects of this changing environmental landscape are a critical public health concern. Wildfires pose both acute and chronic health threats. In addition to mortality, exposure to wildfire smoke has been correlated with morbidities such as cancer, cardiovascular disease, and respiratory syndromes. As the risk and extent of wildfires continues to increase, more research is needed to identify biomarkers of exposure, longitudinal health outcomes, and adaptation in populations who are exposed. Epigenetic modifications to DNA have emerged as biomarkers of exposure, health and disease, and are a focus of this new proposal, as well as future work that will be possible through new data collection as described in this R21 application. DNA methylation, one type of epigenetic modification, does not change the underlying sequence, but can alter genome expression. We will utilize a large multi-ethnic cohort of approximately 5,000 adults recruited from the East Bay area in northern California for whom biospecimens and health data were collected at two time points during 2020-2021 when numerous wildfires occurred across the Western US. We will pursue study Aims that address critical barriers to understanding the relationship between exposure to wildfire smoke, epigenetic changes and health outcomes, through the additional collection of comprehensive data to significantly expand the utility of this unique research resource. Specifically, we will: 1) Develop comprehensive wildfire exposure assignments for all cohort members; 2) Collect additional health outcomes, lifestyle and exposure data from all cohort members; and 3) Perform a pilot study of 400 cohort members to evaluate the relationship between exposure to wildfire smoke and DNA methylation, including epigenetic estimates of biological age. We hypothesize that exposure to wildfire smoke is associated with changes to the DNA methylome. Further, we hypothesize that exposure to wildfire smoke is associated with a greater epigenetic age. A comprehensive and integrated approach to particulate matter- associated changes in DNA methylation could help provide the rationale for intervention strategies to reduce health risks, especially in susceptible individuals, with a significant impact on public health. Epigenetic mechanisms are thought to have a central role, not only as relevant elements of pathogenic mechanisms, but can be considered as mediators of the body adaptation to environmental stimuli, such as air pollutants from exposure to wildfires.
