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. 2015 Aug;123(8):759-65.
doi: 10.1289/ehp.1307824. Epub 2015 Mar 13.

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

Marie-Abele C Bind  1 , Brent A Coull, Annette Peters, Andrea A Baccarelli, Letizia Tarantini, Laura Cantone, Pantel S Vokonas, Petros Koutrakis, Joel D Schwartz
Affiliations

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

Marie-Abele C Bind et al. Environ Health Perspect. 2015 Aug.

Abstract

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, PM2.5 (diameter ≤ 2.5 μm)black carbon, and PM2.5 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, PM2.5 black carbon, and PM2.5 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/m3 increase in PM2.5 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.

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Conflict of interest statement

The authors declare they have no actual or potential competing financial interests.

Figures

Figure 1
Figure 1
Absolute difference in gene-specific methylation (expressed in %5mC with 95% CI) associated with an IQR increase in exposure [interquartile range (IQR) = 14,599 per cm3 for particle number (PN), 0.26 μg/m3 for PM2.5 black carbon, and 3.4 μg/m3 for PM2.5 mass], according to the deciles of the methylation distribution.
Figure 2
Figure 2
Empirical IFN-γ methylation distribution and its associated predicted distribution assuming an IQR increase in particle number concentration. Abbreviations: IQR, interquartile range; PN, particle number.The results show that instead of air pollution being associated with a shifting of the entire distribution to the left, it is associated with a distortion of its shape, increasing in particular the probabilities of lower methylation levels.
See this image and copyright information in PMC

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