Association Between Immune-Related Disease and Allergic Rhinitis: A Two-Sample Mendelian Randomization Study

Background: Immune-related diseases can interact with each other, and growing evidence suggests that these diseases are associated with allergic rhinitis (AR). However, it is unclear whether previously observed associations reflect causal relationships. Objective: This study estimated the genetic association between various immune-related diseases and AR using two-sample Mendelian randomization (MR). Methods: Eight immune-related diseases were selected as exposure factors, and AR was selected as the outcome. The 8 immune-related disease categories included atopic dermatitis (AD), Graves' disease (GD), asthma, Crohn's disease (CD), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ulcerative colitis (UC). Data from GWAS (Genome-Wide Association Studies) were selected to construct instrumental variables (IVs) for each disease, and multiple single-nucleotide polymorphisms (SNPs) were selected as IVs. Corresponding data were retrieved according to the selected SNPs, and all data were summarized and analyzed. Results: A total of 416 SNPs were screened as IVs, and the results of IVW support a causal relationship between AR risk and AD (OR: 1.026, 95% CI: 1.014-1.038, P= 9.59 x 10(-6)), asthma (OR: 1.057, 95% CI: 1.029-1.086, P =.0001), and CD (OR: 1.006, 95% CI: 1.002-1.011, P=.0085). Furthermore, GD (OR: 0.995, 95% CI: 0.991-0.999, P =.0213) and SLE (OR: 0.997, 95% CI: 0.995-1.000, P =.025) may be protective factors. Conclusion: This MR study found that AD, asthma and CD increase the risk of AR in populations of European ancestry, GD and SLE may be protective factors. These results suggest that confounding factors may have influenced associations previously reported in observational studies.