Zhang Ming, Wang Yidian, Hu Shouye, Wu Yue
Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of General Medicine, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Sci Rep. 2025 Jan 2;15(1):135. doi: 10.1038/s41598-024-83880-9.
Air pollution is strongly associated with autoimmune diseases (ADs), however, the genetic causality between them remains poorly understood. Therefore, the aim of this study is to determine the relationship between common air pollutants and ADs through Mendelian randomization (MR) analysis. We conducted a MR study using aggregated data from publicly available genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) associated with 5 common air pollutants are used as instrumental variables. Random-effects inverse variance weighted (IVW) is used as the primary method to assess causal relationships, with results reported in terms of odds ratios (OR). In addition, we used a two-step MR to assess the mediating role of common risk factors for ADs in the effects of air pollution on ADs. Our analysis revealed causal associations between selected air pollutants and specific ADs. Exposure to nitrogen oxides was positively associated with the risk of rheumatoid arthritis (RA) (OR = 1.47,95% CI 1.01-2.14, P = 0.043), Sjogren's syndrome (SS) (OR = 2.29,95% CI 1.08-4.89, P = 0.032), and systemic lupus erythematosus (OR = 7.26,95% CI 2.25-23.40, P = 9.10E-04). Genetically predicted PM2.5 and PM10 were risk factors for ulcerative colitis (OR = 1.68,95% CI 1.05-2.68, P = 0.032) and psoriasis (OR = 1.34,95% CI 1.02-1.76, P = 0.037), respectively. Our results also suggest a negative causal relationship between PM2.5-10 and SS (OR = 0.29, 95% CI 0.10-0.90, P = 0.032). In risk factor-related mediation analyses, BMI and smoking mediated 6% (95% CI 1-10%) and 9% (95% CI 2-17%) of the effect of nitrogen oxides on RA, respectively. This study provides evidence of a causal relationship between air pollutants and specific ADs risks, suggesting that improving air pollution may be important in preventing ADs.
空气污染与自身免疫性疾病（ADs）密切相关，然而，它们之间的遗传因果关系仍知之甚少。因此，本研究的目的是通过孟德尔随机化（MR）分析来确定常见空气污染物与ADs之间的关系。我们使用公开可用的全基因组关联研究（GWAS）的汇总数据进行了一项MR研究。与5种常见空气污染物相关的单核苷酸多态性（SNPs）被用作工具变量。随机效应逆方差加权（IVW）被用作评估因果关系的主要方法，结果以优势比（OR）表示。此外，我们使用两步MR来评估ADs常见风险因素在空气污染对ADs影响中的中介作用。我们的分析揭示了所选空气污染物与特定ADs之间的因果关联。接触氮氧化物与类风湿性关节炎（RA）风险呈正相关（OR = 1.47，95%CI 1.01 - 2.14，P = 0.043）、干燥综合征（SS）（OR = 2.29，95%CI 1.08 - 4.89，P = 0.032）和系统性红斑狼疮（OR = 7.26，95%CI 2.25 - 23.40，P = 9.10E - 04）。基因预测的PM2.5和PM10分别是溃疡性结肠炎（OR = 1.68，95%CI 1.05 - 2.68，P = 0.032）和银屑病（OR = 1.34，95%CI 1.02 - 1.76，P = 0.037）的危险因素。我们的结果还表明PM2.5 - 10与SS之间存在负因果关系（OR = 0.29，95%CI 0.10 - 0.90，P = 0.032）。在与风险因素相关的中介分析中，体重指数（BMI）和吸烟分别介导了氮氧化物对RA影响的6%（95%CI 1 - 10%）和9%（95%CI 2 - 17%）。本研究提供了空气污染物与特定ADs风险之间因果关系的证据，表明改善空气污染对于预防ADs可能很重要。
