Limited Clinical Impact of Genetic Associations between Celiac Disease and Type 2 Inflammatory Diseases: Insights from Mendelian Randomization.

Background: Celiac disease, a gluten-triggered autoimmune disorder, is known for its systemic inflammatory effects. Its genetic associations with type 2 inflammatory diseases like asthma, allergic rhinitis, and atopic dermatitis remain unclear, prompting this study to explore their potential genetic interplay. Methods: Utilizing two-sample Mendelian randomization (TSMR), we examined the genetic associations using 15 genetic instruments from GWAS datasets. Our analysis focused on celiac disease and its relation to asthma, allergic rhinitis, atopic dermatitis, and IgE-mediated food allergies. A power analysis was conducted to determine the study's detection capabilities, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using various MR methods. Results: Our Mendelian randomization analysis identified statistically significant genetic associations between celiac disease and several type 2 inflammatory diseases, although these were practically insignificant. Specifically, celiac disease was associated with a slight increase in the risk of atopic dermatitis (OR = 1.037) and a minor protective effect against asthma (OR = 0.97). The link with allergic rhinitis was statistically detectable (OR = 1.002) but practically negligible. Despite robust statistical confirmation through various sensitivity analyses, all observed effects remained within the range of practical equivalence (ROPE). Conclusions: Our study identifies potential genetic associations between celiac disease and certain type 2 inflammatory diseases. However, these associations, predominantly within the ROPE range, suggest only limited clinical implications. These findings highlight the need for cautious interpretation and indicate that further exploration for clinical applications may not be warranted at this stage.