Background

Telomere length (TL) is a biomarker of genomic aging. The evidence on the association between TL and air pollution was inconsistent. Besides, the modification effect of genetic susceptibility on the air pollution-TL association remains unknown.

Objective

We aimed to evaluate the association of ambient air pollution with TL and further assess the modification effect of genetic susceptibility.

Methods

433,535 participants with complete data of TL and air pollutants in UK Biobank were included. Annual average exposure of NO₂, NO_x, PM₁₀ and PM_2.5 was estimated by applying land use regression models. Genetic risk score (GRS) was constructed using reported telomere-related SNPs. Leukocyte TL was measured by quantitative polymerase chain reaction (qPCR). Multivariable linear regression models were employed to conduct associational analyses.

Results

Categorical exposure models and RCS models both indicated U-shaped (for NO₂ and NO_x) and L-shaped (for PM₁₀ and PM_2.5) correlations between air pollution and TL. In comparison to the lowest quartile, the 2nd and 3rd quartile of NO₂ (q2: −1.3% [−2.1%, −0.4%]; q3: −1.2% [−2.0%, −0.3%], NO_x (q2: −1.3% [−2.1%, −0.5%]; q3: −1.4% [−2.2%, −0.5%]), PM_2.5 (q2: −0.8% [−1.7%, 0.0%]; q3: −1.3% [−2.2%, −0.5%]), and the third quartile of PM₁₀ (q3: −1.1% [−1.9%, −0.2%]) were inversely associated with TL. The highest quartile of NO₂ was positively correlated with TL (q4: 1.0% [0.0%, 2.0%]), whereas the negative correlation between the highest quartile of other pollutants and TL was also attenuated and no longer significant. In the genetic analyses, synergistic interactions were observed between the 4th quartile of three air pollutants (NO₂, NO_x, and PM_2.5) and genetic risk.

Impact statement

Our study for the first time revealed a non-linear trend for the association between air pollution and telomere length. The genetic analyses suggested synergistic interactions between air pollution and genetic risk on the air pollution-TL association. These findings may shed new light on air pollution’s health effects, offer suggestions for identifying at-risk individuals, and provide hints regarding further investigation into gene-environment interactions.

中文翻译：

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英国生物样本库中的环境空气污染、遗传风险和端粒长度

背景

端粒长度（TL）是基因组衰老的生物标志物。关于 TL 与空气污染之间关联的证据并不一致。此外，遗传易感性对空气污染-TL关联的修饰作用仍不清楚。

客观的

我们的目的是评估环境空气污染与TL的关联，并进一步评估遗传易感性的改变效应。

方法

纳入了英国生物银行中拥有完整 TL 和空气污染物数据的 433,535 名参与者。通过应用土地利用回归模型估算NO ₂、NO _x、PM ₁₀和PM _{2.5的年平均暴露量。}使用报告的端粒相关 SNP 构建遗传风险评分 (GRS)。通过定量聚合酶链式反应 (qPCR) 测量白细胞 TL。采用多变量线性回归模型进行关联分析。

结果

分类暴露模型和RCS模型均表明空气污染与TL之间存在U形（对于NO ₂和NO _x）和L形（对于PM ₁₀和PM _{2.5 ）相关性。}与最低四分位数相比，NO ₂的第二和第三四分位数(q2: -1.3% [-2.1%, -0.4%]; q3: -1.2% [-2.0%, -0.3%], NO x ₍ q2 ：−1.3%[−2.1%，−0.5%]；q3：−1.4%[−2.2%，−0.5%]），PM _2.5（q2：−0.8%[−1.7%，0.0%]；q3：− 1.3% [−2.2%, -0.5%]) 和 PM ₁₀的第三个四分位数(q3: -1.1% [−1.9%, -0.2%]) 与 TL 呈负相关。NO ₂的最高四分位数呈正相关与 TL 相关（q4：1.0% [0.0%, 2.0%]），而其他污染物最高四分位数与 TL 之间的负相关性也减弱，不再显着。遗传分析中，观察到第 4 个污染物之间存在协同相互作用。三种空气污染物（NO ₂、NO _x和 PM _2.5）的四分位数和遗传风险。

影响报告

我们的研究首次揭示了空气污染与端粒长度之间的非线性趋势。遗传分析表明空气污染和遗传风险之间在空气污染-TL 关联上存在协同相互作用。这些发现可能为空气污染对健康的影响提供新的线索，为识别高危个体提供建议，并为进一步调查基因与环境相互作用提供线索。