Abstract：
The correlation between air pollution and neurodegenerative diseases has garnered growing attention. Although observational studies have indicated a potential link between air pollution and neurodegenerative disease, establishing a causal relationship remains uncertain. To address this gap, we performed a two-sample Mendelian randomization analysis utilizing genetic instruments. This analysis aimed to investigate the causal connections between PM2.5, PM10, NO2, and NOX exposure and the occurrence of Parkinson\'s disease (PD) and Alzheimer\'s disease (AD). We implemented a series of filtering steps to identify suitable genetic instruments that demonstrated significant associations (P < 5 × 10-8) with PM2.5, PM10, NO2, and NOX. These instruments were derived from a comprehensive genome-wide association study (GWAS) encompassing up to 456,380 participants in the UK Biobank. To obtain summary statistics for PD (N = 482,730) and AD risk (N = 63,926), we utilized the most recent GWAS datasets available. For our primary analysis, we employed the inverse-variance weighted approach for two-sample MR. A multivariable MR (MVMR) was also performed to verify the impact of air pollution exposure on the risk of PD and AD. To ensure the robustness of our findings, sensitivity analyses and heterogeneity assessments were performed. In two-sample MR, by employing the inverse-variance weighted method, our result suggested that genetically NO2 exposure showed a significant association with an elevated risk of PD (OR = 4.07, 95% CI: 1.13 to 19.62, P = 0.034) and genetically PM10 exposure exhibited a significant association with a heightened risk of AD (OR = 1.93, 95% CI: 1.03-3.59, P = 0.040). Further MVMR analysis demonstrated that the causal effect between NO2 and PD disappeared (OR = 3.489, 95% CI: 0.01 to 2.1e + 03, P = 0.703), and only PM10 was associated with an increased risk of AD (OR = 6.500, 95% CI: 1.10 to 38.51, P = 0.039). Sensitivity analysis showed no detectable heterogeneity and pleiotropy (P > 0.05). Our findings demonstrate that NO2 and PM10 exposure may contribute to a risk of PD and AD, respectively. Future research is necessary to elucidate potential physiopathological mechanisms.
摘要：
空气污染与神经退行性疾病之间的相关性已引起越来越多的关注。尽管观察研究表明空气污染与神经退行性疾病之间存在潜在联系，建立因果关系仍然不确定。为了解决这个差距，我们利用遗传仪器进行了双样本孟德尔随机化分析.该分析旨在研究PM2.5，PM10，NO2和NOX暴露与帕金森病（PD）和阿尔茨海默病（AD）发生之间的因果关系。我们实施了一系列过滤步骤，以确定与PM2.5，PM10，NO2和NOX显着相关（P<5×10-8）的合适遗传工具。这些仪器来自一项全面的全基因组关联研究（GWAS），该研究涵盖了英国生物库的多达456,380名参与者。为了获得PD(N=482,730)和AD风险(N=63,926)的汇总统计数据，我们利用了可用的最新GWAS数据集。对于我们的初步分析，我们对两样本MR采用了逆方差加权方法。还进行了多变量MR（MVMR）以验证空气污染暴露对PD和AD风险的影响。为了确保我们发现的稳健性，进行了敏感性分析和异质性评估.在双样本MR中，通过采用逆方差加权法，我们的结果表明,NO2基因暴露与PD风险升高显著相关(OR=4.07,95%CI:1.13~19.62,P=0.034),PM10基因暴露与AD风险升高显著相关(OR=1.93,95%CI:1.03~3.59,P=0.040).进一步的MVMR分析表明，NO2和PD之间的因果关系消失（OR=3.489，95％CI：0.01至2.1e03，P=0.703），只有PM10与AD风险增加相关(OR=6.500,95%CI:1.10~38.51,P=0.039)。敏感性分析未发现异质性和多效性(P>0.05)。我们的研究结果表明，NO2和PM10暴露可能导致PD和AD的风险。分别。未来的研究对于阐明潜在的病理生理学机制是必要的。
