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.

Grant Number: 1R21ES037100-01
NIH Institute/Center: NIH
Principal Investigator: LISA BARCELLOS