Abstract
BACKGROUND AND AIM[|]Previous studies have suggested that smokers may have higher susceptibility to air pollution-related morbidity and mortality. However, the biological mechanisms are poorly understood. We sought to elucidate whether air pollution impacts health outcomes via epigenetic modification in a racially and ethnically diverse population of smokers.[¤]METHOD[|]We conducted an epigenome-wide association study (EWAS) of air pollution among 843 Los Angeles-based smokers from the Multiethnic Cohort Study (361 African American, 82 Japanese American, 395 Latino, and 5 White participants). Blood DNA methylation was measured using the MethylationEPICv1 array. Exposures to kriging-interpolated PM2.5, PM10, NO2, and NOx averaged twelve months prior to blood draw (1994-2006) were estimated based on participants’ addresses. Linear regression was conducted to assess the association between each pollutant and DNA methylation, adjusting for race and ethnicity, age, sex, neighborhood SES, and cell type proportions. Race- and ethnicity-specific EWAS were conducted for African Americans and Latinos.[¤]RESULTS[|]Average levels of all pollutants were significantly higher among Latinos compared to the other races and ethnicities (p<0.0001). Among all participants, there were no statistically significant associations between any pollutant and DNA methylation (genome-wide p<9×10⁻⁸). In the African American-specific EWAS, the highest quartile (Q4 vs Q1) of NO2 was associated with differential methylation at 42 CpG sites (p<9×10⁻⁸). The most significant hits were in genes associated with cancer risk/survival, including ATP9B (cg14071758), PEMT (cg10633334), WIZ (cg01387972) and TRIM27 (cg22355525). In the Latino-specific EWAS, the highest quartile (Q4 vs Q1) of NO2 was associated with decreased DNA methylation at cg03020635 in chromosome 14 (p<9×10⁻⁸). The effect estimates for these CpG sites were heterogeneous between African Americans and Latinos (p-heterogeneity<0.0001).[¤]CONCLUSIONS[|]Among African Americans, NO2 was associated with differential methylation at several CpG sites in cancer-related genes. The heterogeneous associations by race and ethnicity suggest potential racial- and ethnic-specific epigenetic changes due to air pollution among smokers.[¤]