Causal relationship between multiple sclerosis and asthma and chronic obstructive pulmonary disease based on genome-wide association study data

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.