The Nasal Methylome as Biomarker of PM2.5 Exposure in Children

Abstract

Background: The nasal methylome is easily accessible and in direct contact with the environment, potentially serving as an epigenetic biomarker. Methods: We conducted nasal epigenome-wide association analyses of exposure to ambient fine particulate matter (PM2.5) within the Project Viva cohort among 503 children (mean age 12.9 y). We used residential addresses to estimate daily ambient PM2.5 levels with 1km resolution during the day of sample collection, 7-days and 1-year prior moving average (MA). Trained personnel collected nasal swabs from the anterior nares and DNA methylation (DNAm) was measured using the Illumina MethylationEPIC BeadChip. We tested 701,812 high quality autosomal CpGs conducting CpG-by-CpG and regional DNAm analyses. We adjusted for maternal education, smokers living in the household, child sex, race/ethnicity, BMI z-score, age, season at sample collection, heterogeneity driven by cell-type and accounted for multiple comparisons. Additionally, we evaluated the ability to predict PM2.5 exposure by DNAm marks using LASSO. Results: Mean (SD) PM2.5 levels during the day of sample collection, 1-week, and 1-year prior were 7.44 (3.04), 7.43 (2.02) and 7.76 (0.55) μg/m3, respectively. Adjusted analyses identified 6,220 CpGs associated with 1-year PM2.5 levels (FDR<0.05), including 80 CpGs passing Bonferroni correction (P<7.1x10-8), and 30 differentially methylated regions (FDR<0.05) having 10 or more CpGs. Results included genes previously associated with PM2.5 in an EWAS of adult blood (ANKHD1, ANKRD11). Using 80% of the data for training (N=402), we identified 17 CpGs that moderately predicted 1-year PM2.5 levels (r=0.44) in the remaining validation set (N=101). Conclusion: We observed widespread nasal DNAm variability associated with ambient PM2.5 levels 1-year prior to sample collection but no associations with short term levels. The nasal methylome may serve as a sensitive epigenetic biomarker of long-term PM2.5 exposure.