Causal relationship between asthma and inflammatory bowel disease: A two-sample bidirectional mendelian randomization analysis

Abstract

Background Based on the findings of current observational studies, asthma and inflammatory bowel disease (including Crohn's disease and ulcerative colitis) are associated; however, their causal association cannot be established due to methodological limitations. Therefore, we use two-sample bidirectional mendelian randomization (MR) to overcome the confounding factors and explore the causal link between the two diseases. Methods After selecting asthma and IBD-related genome-wide association studies (GWAS) data and screening single nucleotide polymorphisms (SNPs), MR analysis was performed by four methods: inverse variance weighted (IVW), MR-Egger, maximum likelihood, and weighted median (WM), while Cochran's Q test was used to detect heterogeneity and MR-Egger intercept to detect horizontal pleiotropy. Finally, we used the leave-one-out method and funnel plot to perform sensitivity analysis. Results We screened 57, 59, and 60 SNPs in the association analysis of asthma and IBD, CD, and UC, respectively. The results of MR analysis showed that asthma only increased the risk of CD (IVW: OR = 1.1712, 95% CI = 1.0418–1.3167, P value = 0.0082; maximum likelihood: OR = 1.1739, 95% CI = 1.0428–1.3215, P value = 0.0080). In reverse MR analysis, there may be suggestive positive results for IBD and asthma despite not meeting the Bonferroni correction (IVW: OR = 1.0165, 95% CI = 1.0023–1.0333, P value = 0.0222; maximum likelihood: OR = 1.0168, 95% CI = 1.0025–1.0314, P value = 0.0212). Neither forward nor reverse MR analysis revealed heterogeneity or horizontal pleiotropy. Similarly, we did not find potential directional pleiotropy by funnel plot, and the leave-one-out method did not suggest a significant effect of a single SNP on the overall results. Conclusions Our study found that asthmatic patients had a higher risk of CD, suggesting that there may be a common pathophysiological process between asthma and CD.