Causal Effects of Inflammatory Bowel Disease on Lung Function and Disease: A Two-Sample Mendelian Randomization Study.

BACKGROUND AND AIMS: The increasing prevalence of Crohn's disease (CD) and ulcerative colitis (UC)-the two main forms of inflammatory bowel disease (IBD)-has made these conditions a growing concern in global public health. While IBD primarily impacts the gastrointestinal tract, emerging evidence suggests its extraintestinal effects, especially on the respiratory system. The correlation between the lungs and the gastrointestinal system has drawn attention to the potential pulmonary complications in IBD patients. The causal link between IBD and lung function or related disease remains inconclusive.

METHODS

Leveraging publicly available genome-wide association study (GWAS) data sets, we performed a two-sample Mendelian randomization analysis to investigate potential links between ulcerative colitis, Crohn's disease, and various aspects of lung function or respiratory illness. Through meticulous quality control measures, we pinpointed SNPs with robust associations to UC and CD. The inverse-variance weighted method was our primary analytic approach. Additionally, we evaluated heterogeneity, explored potential pleiotropy, and performed sensitivity tests.

RESULTS

We conducted an analysis using GWAS data obtained from the European population, identifying 54 and 77 SNPs for association studies related to lung function and disease in UC and CD, respectively. The results from the MR analysis revealed that neither UC nor CD exhibited a discernible impact on lung function, encompassing metrics such as total lung volume, forced vital capacity, forced expiratory volume in the first second, the forced vital capacity/forced expiratory volume in the first second ratio, and peak expiratory flow. Additionally, neither UC nor CD demonstrated an elevated risk of idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, or pulmonary cancer. In contrast, CD presented a heightened risk of asthma compared to UC.

CONCLUSION

CD has been associated with a higher risk of developing asthma in the European population.