May 10, 2025

Prenatal Ambient Air Pollution Associations With DNA Methylation in Asthma and Allergy Relevant Genes: Findings from ECHO

Meredith Palmore, Emma E Thompson, Fang Fang et al. Environmental Epigenetics, 2025;, dvaf013, https://doi.org/10.1093/eep/dvaf013

ABSTRACT
Background
Prenatal exposure to air pollution is an important risk factor for child health outcomes, including asthma. Identification of DNA methylation changes associated with air pollutant exposure can provide new intervention targets to improve children’s health.

Objectives
To test the association between prenatal air pollutant exposure and DNA methylation in developmental and asthma/allergy relevant biospecimens (placenta, buccal, cord blood, nasal mucosa, and lavage).

Methods
A subset of 2,294 biospecimens collected from 1,906 child participants enrolled in the Environmental Influences on Child Health Outcomes (ECHO) program with prenatal air pollutant and high-quality Illumina Asthma&Allergy DNA methylation array measures (n=37,197 probes) were included. Prenatal ozone, nitrogen dioxide, and fine particulate matter were derived using residential history during pregnancy and spatiotemporal models. For each pollutant, biospecimen type, and prenatal exposure window, we estimated the effects of air pollution on gene DNA methylation levels. We compared results across pollutants, biospecimen types, and trimesters, and tested for critical months of exposure using distributed lag models.

Results
Conceptual overview for how genes were categorized into distributed lag result types
DNA methylation levels at 154 out of 4,746 tested genes were associated with air pollution; over 95% were exposure window, pollutant, and biospecimen type specific. The fewest gene associations were detected in trimester 2, relative to other exposure windows. A variety of trends in methylation patterns were observed in response to lagged monthly pollution levels.

Conclusions
Child DNA methylation changes at specific respiratory and immune relevant genes are associated with prenatal air pollutant exposures. Future studies should examine the relationship between these pollution-sensitive genes and child health.

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