Beyond the Mean: Quantile Regression to Explore the Association of Air Pollution with Gene-Specific Methylation in the Normative Aging Study

BACKGROUND: Air pollution has been related to mean changes in outcomes, including DNA methylation. However, mean regression analyses may not capture associations that occur primarily in the tails of the outcome distribution. OBJECTIVES: In this study, we examined whether the association between particulate air pollution and DNA methylation differs across quantiles of the methylation distribution. We focused on methylation of candidate genes related to coagulation and inflammation: coagulation factor III (F3), intercellular adhesion molecule 1 (ICAM-1), interferon gamma (IFN-γ), interleukin-6 (IL-6), and toll-like receptor 2 (TRL-2). METHODS: We measured gene-specific blood DNA methylation repeatedly in 777 elderly men participating in the Normative Aging Study (1999–2010). We fit quantile regressions for longitudinal data to investigate whether the associations of particle number, PM(2.5) (diameter ≤ 2.5 μm)black carbon, and PM(2.5) mass concentrations (4-week moving average) with DNA methylation [expressed as the percentage of methylated cytosines over the sum of methylated and unmethylated cytosines at position 5 (%5mC)] varied across deciles of the methylation distribution. We reported the quantile regression coefficients that corresponded to absolute differences in DNA methylation (expressed in %5mC) associated with an interquartile range increase in air pollution concentration. RESULTS: Interquartile range increases in particle number, PM(2.5) black carbon, and PM(2.5) mass concentrations were associated with significantly lower methylation in the lower tails of the IFN-γ and ICAM-1 methylation distributions. For instance, a 3.4-μg/m(3) increase in PM(2.5) mass concentration was associated with a 0.18%5mC (95% CI: –0.30, –0.06) decrease on the 20th percentile of ICAM-1 methylation, but was not significantly related to the 80th percentile (estimate: 0.07%5mC, 95% CI: –0.09, 0.24). CONCLUSIONS: In our study population of older men, air pollution exposures were associated with a left shift in the lower tails of the IFN-γ and ICAM-1 methylation distributions. CITATION: Bind MA, Coull BA, Peters A, Baccarelli AA, Tarantini L, Cantone L, Vokonas PS, Koutrakis P, Schwartz JD. 2015. Beyond the mean: quantile regression to explore the association of air pollution with gene-specific methylation in the Normative Aging Study. Environ Health Perspect 123:759–765; http://dx.doi.org/10.1289/ehp.1307824