Cui Wenhui, Wu Tingting, Shi Keqing, Wang Xin, Chen Shuyu, Cao Mengjun, Xu Aolong, Chong Yingzhi, Zhang Xueli, Wang Qiang
College of Public Health, Shandong Second Medical University, Weifang, Shandong, China.
Department of Public Health, Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, China.
Medicine (Baltimore). 2025 Sep 12;104(37):e44473. doi: 10.1097/MD.0000000000044473.
This study aimed to assess potential causal relationship between Multiple sclerosis (MS) and asthma and Chronic obstructive pulmonary disease (COPD) using Mendelian randomization (MR). In order to investigate the causal relationship, a 2 -sample MR study was conducted with both a training set and a validation set. The genetic variation data for MS, asthma, and COPD were all from published genome-wide association studies (GWAS) in European individuals. Inverse variance weighted (IVW) was main MR analysis method. Weighted median, MR-Egger regression, weighted mode and simple mode were used as auxiliary methods. Two-sided P < .05 was nominally significant, P < .025 = 0.05/(1 exposure × 2 outcomes) was Bonferroni significant for main MR analysis. The Cochran Q test, MR-Egger intercept, and MR-PRESSO global test were used to assess heterogeneity and horizontal pleiotropy. Leave-one-out analysis was used to evaluate the impact of removing a single SNP on causal relationship estimate. There was a negative causal relationship between MS and asthma (IVW: odds ratio [OR] = 0.969, 95% CI: 0.949-0.990, P = .004). However, this relationship was not confirmed in validation set (IVW: OR = 1.010, 95% CI: 0.986-1.034, P = .428). In the training and validation sets, no significant causal relationship between MS and COPD was found (P > .05). The Cochran Q test indicated no heterogeneity, and both the MR-Egger intercept and MR-PRESSO global test showed no horizontal pleiotropy. The leave-one-out analysis showed robustness of the MR results. This study provides meaningful insights into causal relationship between MS and asthma and COPD and provides important theoretical basis for personalized treatment of MS.
本研究旨在利用孟德尔随机化（MR）评估多发性硬化症（MS）与哮喘及慢性阻塞性肺疾病（COPD）之间的潜在因果关系。为了探究因果关系，进行了一项双样本MR研究，包括一个训练集和一个验证集。MS、哮喘和COPD的基因变异数据均来自已发表的欧洲个体全基因组关联研究（GWAS）。逆方差加权（IVW）是主要的MR分析方法。加权中位数、MR-Egger回归、加权模式和简单模式用作辅助方法。双侧P<0.05为名义显著性，P<0.025 = 0.05/（1暴露×2结局）对主要MR分析具有Bonferroni显著性。采用Cochran Q检验、MR-Egger截距和MR-PRESSO全局检验评估异质性和水平多效性。采用留一法分析评估去除单个单核苷酸多态性（SNP）对因果关系估计的影响。MS与哮喘之间存在负向因果关系（IVW：比值比[OR]=0.969，95%置信区间：0.949 - 0.990，P = 0.004）。然而，该关系在验证集中未得到证实（IVW：OR = 1.010，95%置信区间：0.986 - 1.034，P = 0.428）。在训练集和验证集中，未发现MS与COPD之间存在显著因果关系（P>0.05）。Cochran Q检验表明无异质性，MR-Egger截距和MR-PRESSO全局检验均未显示水平多效性。留一法分析显示MR结果具有稳健性。本研究为MS与哮喘及COPD之间的因果关系提供了有意义的见解，并为MS的个性化治疗提供了重要的理论依据。
