Abstract

Background:

Few epigenome-wide association studies (EWAS) on air pollutants exist, and none have been done on transportation noise exposures, which also contribute to environmental burden of disease.

Objective:

We performed mutually independent EWAS on transportation noise and air pollution exposures.

Methods:

We used data from two time points of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) from 1,389 participants contributing 2,542 observations. We applied multiexposure linear mixed-effects regressions with participant-level random intercept to identify significant Cytosine-phosphate-Guanine (CpG) sites and differentially methylated regions (DMRs) in relation to 1-y average aircraft, railway, and road traffic day-evening-night noise (Lden); nitrogen dioxide (${\mathrm{NO}}_2$); and particulate matter (PM) with aerodynamic diameter $<2.5\mathrm{\mu }\mathrm{m}$ (${\mathrm{PM}}_{2.5}$). We performed candidate (CpG-based; cross-systemic phenotypes, combined into “allostatic load”) and agnostic (DMR-based) pathway enrichment tests, and replicated previously reported air pollution EWAS signals.

Results:

We found no statistically significant CpGs at false discovery rate $<0.05$. However, 14, 48, 183, 8, and 71 DMRs independently associated with aircraft, railway, and road traffic Lden; ${\mathrm{NO}}_2$; and ${\mathrm{PM}}_{2.5}$, respectively, with minimally overlapping signals. Transportation Lden and air pollutants tendentially associated with decreased and increased methylation, respectively. We observed significant enrichment of candidate DNA methylation related to C-reactive protein and body mass index (aircraft, road traffic Lden, and ${\mathrm{PM}}_{2.5}$), renal function and “allostatic load” (all exposures). Agnostic functional networks related to cellular immunity, gene expression, cell growth/proliferation, cardiovascular, auditory, embryonic, and neurological systems development were enriched. We replicated increased methylation in cg08500171 (${\mathrm{NO}}_2$) and decreased methylation in cg17629796 (${\mathrm{PM}}_{2.5}$).

Conclusions:

Mutually independent DNA methylation was associated with source-specific transportation noise and air pollution exposures, with distinct and shared enrichments for pathways related to inflammation, cellular development, and immune responses. These findings contribute in clarifying the pathways linking these exposures and age-related diseases but need further confirmation in the context of mediation analyses. https://doi.org/10.1289/EHP6174

中文翻译：

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外周血中的全基因组 DNA 甲基化和长期暴露于特定来源的运输噪声和空气污染：SAPALDIA 研究。

摘要

背景：

很少有关于空气污染物的表观基因组关联研究 (EWAS)，也没有关于交通噪声暴露的研究，这也导致了疾病的环境负担。

客观的：

我们对交通噪声和空气污染暴露进行了相互独立的 EWAS。

方法：

我们使用了瑞士成人空气污染和肺和心脏病队列研究 (SAPALDIA) 的两个时间点的数据，这些数据来自 1,389 名参与者，提供了 2,542 次观察。我们应用多重曝光线性混合效应回归和参与者级别的随机截距来识别与 1 年平均飞机、铁路和道路交通日晚相关的显着胞嘧啶-磷酸-鸟嘌呤 (CpG) 位点和差异甲基化区域 (DMR) -夜间噪音（Lden）；二氧化氮 （${\mathrm{不}}_2$); 和具有空气动力学直径的颗粒物 (PM)$<2.5\mathrm{\mu }\mathrm{米}$(${\mathrm{下午}}_{2.5}$）。我们进行了候选（基于 CpG；跨系统表型，组合成“allostatic load”）和不可知（基于 DMR）通路富集测试，并复制了先前报告的空气污染 EWAS 信号。

结果：

我们在错误发现率下没有发现具有统计学意义的 CpG $<0.05$. 然而，14、48、183、8 和 71 个 DMR 与飞机、铁路和道路交通 Lden 独立相关；${\mathrm{不}}_2$; 和${\mathrm{下午}}_{2.5}$，分别具有最小重叠信号。运输 Lden 和空气污染物倾向于分别与甲基化减少和增加有关。我们观察到与 C 反应蛋白和体重指数（飞机、道路交通 Lden 和${\mathrm{下午}}_{2.5}$)、肾功能和“平衡负荷”（所有暴露）。丰富了与细胞免疫、基因表达、细胞生长/增殖、心血管、听觉、胚胎和神经系统发育相关的不可知论功能网络。我们在 cg08500171 中复制了增加的甲基化（${\mathrm{不}}_2$) 和 cg17629796 (${\mathrm{下午}}_{2.5}$）。

结论：

相互独立的 DNA 甲基化与特定来源的运输噪声和空气污染暴露相关，与炎症、细胞发育和免疫反应相关的途径具有独特和共同的富集。这些发现有助于阐明将这些暴露与年龄相关疾病联系起来的途径，但需要在中介分析的背景下进一步确认。https://doi.org/10.1289/EHP6174