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Estimated effects of Short-term Controlled Ozone Exposure on DNA Methylation of Genes Related to Lung Functions

Presented by:
Anqi Wang (The Pennsylvania State University)

As energy use and production rises globally, air quality has become a concerning issue as about 545 million people globally suffer from chronic respiratory disease, corresponding to a 39.8% increase since 1990. As a result, estimating the effects of air pollutants on lung functions is crucial for improving public health. Major pollutants such as ozone have been identified to be associated with increased respiratory inflammation and decreased lung functions; however, association does not imply causation, and all statistical analyses regarding ozone effects on lung functions published by far are on studies that are observational and non-randomized. Consequently, issues of non-randomized observational studies such as biases and confounding variables would arise and hinder statisticians' ability to conclude whether there is a causal effect of ozone on decreased lung functions. Nonetheless, a randomized and controlled crossover experiment of 17 young and healthy individuals has been conducted recently to investigate the impact of short-term ozone (vs. clean air) exposure on the genome-wide DNA methylation of target bronchial epithelial cells. DNA methylation was measured because prior non-randomized studies suggest air pollutants are associated with epigenetic changes such as DNA methylation at genes that are related to lung functions, inflammation, and oxidative stress. Since DNA methylation predominantly takes place at cytosine-guanine(CpG) dinucleotides, DNA methylation level is measured at CpG islands of genes, which impacts the silencing of gene expression. By applying statistical tools such as Fisher exact p-values, 95% Fisherian interval, 95% Neymanian (confidence) interval, and multiple testing p-value adjustments, we can conclude causal effects of ozone on lung functions if adjusted p-value for a CpG site of a gene is considered statistically significant(p<0.05). Understanding the causation relationships between air pollutants and DNA methylation of a gene can help us better investigate gene expression mechanisms and the underlying biological pathway that leads to the changes in DNA methylation patterns of lung function-related genes. Eventually, that will help us identify individuals with susceptible genotypes and take preventative measures and treatments in the future.