Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
CNS Neurosci Ther. 2024 Jul;30(7):e14812. doi: 10.1111/cns.14812.
Air pollutants have been reported to have a potential relationship with amyotrophic lateral sclerosis (ALS). The causality and underlying mechanism remained unknown despite several existing observational studies. We aimed to investigate the potential causality between air pollutants (PM2.5, NO, and NO) and the risk of ALS and elucidate the underlying mechanisms associated with this relationship.
The data utilized in our study were obtained from publicly available genome-wide association study data sets, in which single nucleotide polymorphisms (SNPs) were employed as the instrumental variantswith three principles. Two-sample Mendelian randomization and transcriptome-wide association (TWAS) analyses were conducted to evaluate the effects of air pollutants on ALS and identify genes associated with both pollutants and ALS, followed by regulatory network prediction.
We observed that exposure to a high level of PM2.5 (OR: 2.40 [95% CI: 1.26-4.57], p = 7.46E-3) and NOx (OR: 2.35 [95% CI: 1.32-4.17], p = 3.65E-3) genetically increased the incidence of ALS in MR analysis, while the effects of NO showed a similar trend but without sufficient significance. In the TWAS analysis, TMEM175 and USP35 turned out to be the genes shared between PM2.5 and ALS in the same direction.
Higher exposure to PM2.5 and NO might causally increase the risk of ALS. Avoiding exposure to air pollutants and air cleaning might be necessary for ALS prevention.
已有研究报道，空气污染物可能与肌萎缩侧索硬化症（ALS）存在潜在关联。尽管已有多项观察性研究，但因果关系及其潜在机制仍不清楚。我们旨在探究空气污染物（PM2.5、NO 和 NOx）与 ALS 风险之间的潜在因果关系，并阐明与这种关系相关的潜在机制。
我们研究所用的数据来自公开的全基因组关联研究数据集，其中单核苷酸多态性（SNP）被用作工具变量，遵循三个原则。我们进行了两样本 Mendelian 随机化和全转录组关联（TWAS）分析，以评估空气污染物对 ALS 的影响，并确定与污染物和 ALS 均相关的基因，然后进行调控网络预测。
我们发现，PM2.5（OR：2.40 [95% CI：1.26-4.57]，p=7.46E-3）和 NOx（OR：2.35 [95% CI：1.32-4.17]，p=3.65E-3）的高水平暴露在 MR 分析中遗传上增加了 ALS 的发病风险，而 NO 的影响则呈现出相似的趋势，但无足够显著意义。在 TWAS 分析中，TMEM175 和 USP35 被证明是 PM2.5 和 ALS 之间具有相同方向的共享基因。
更高水平的 PM2.5 和 NO 可能会导致 ALS 风险增加。为了预防 ALS，可能需要避免接触空气污染物和进行空气净化。
