An epigenome-wide analysis of DNA methylation, racialized and economic inequities, and air pollution

Background: DNA methylation (DNAm) provides a plausible mechanism by which adverse exposures become embodied and contribute to health inequities, due to its role in genome regulation and responsiveness to social and biophysical exposures tied to societal context. However, scant epigenome-wide association studies (EWAS) have included structural and lifecourse measures of exposure, especially in relation to structural discrimination. Our study tested the hypothesis that DNAm is a mechanism by which racial discrimination, economic adversity, and air pollution become biologically embodied, via a series of cross-sectional EWAS, conducted in two population-based samples of US-born Black non-Hispanic (Black NH), white non-Hispanic (white NH), and Hispanic individuals (My Body My Story:: n = 224 Black NH and 69 white NH;; and the Multi-Ethnic Study of Atherosclerosis:: n = 229 Black NH, n = 555 white NH and n = 191 Hispanic). Genome-wide changes in DNAm were measured using the Illumina EPIC BeadChip (MBMS; using frozen blood spots) and Illumina 450 k BeadChip (MESA; using purified monocytes). Results: We observed the strongest associations with traffic-related air pollution (between 0 and 22 DNAm sites associated at p < 2.4e-07, measured via black carbon and nitrogen oxides exposure), with evidence from both studies suggesting that air pollution exposure may induce epigenetic changes related to inflammatory processes. However, we did not replicate previous air pollution EWAS findings. We also found suggestive associations of DNAm variation with measures of structural racial discrimination (e.g. for Black NH participants, in MBMS born in a Jim Crow state associates with a DNAm site in ZNF286B at p = 8.43E-08; and in MESA adult exposure to racialized economic residential segregation associates with a DNAm site in FUT6 at p = 4.05E-08) situated in genes with plausible links to effects on health. Conclusions: Overall, this work suggests that DNAm is a biological mechanism through which structural racism and air pollution (of which distribution of exposure is inequitable) become embodied and may lead to health inequities. Due to the extensive range of exposures we tested, further replication in additional studies and other tissues is warranted.