The genetic interaction between Atopic dermatitis and Celiac disease: A bidirectional two-sample Mendelian randomization study

Background: Multiple previous observational studies have reported inconsistent results in investigating the association between atopic dermatitis (AD) and celiac disease (CD).Observational studies may be inadequate for elucidating potential causal relationships between AD and CD due to the issues of reverse causation and confounding variables. The existence of a bidirectional causal relationship between AD and CD remains unclear. Objective: To investigate the potential bidirectional causal relationship between atopic dermatitis and celiac disease. Methods: Utilizing the summary statistics from large-scale Genome-Wide Association Studies (GWASs) in European populations, we examined the potential bidirectional causal effects between AD and CD through a bidirectional Mendelian randomization analysis. The inverse-variance weighted (IVW) method was employed as the primary analytical approach. The MR-Egger, weighted median, simple mode, and weighted mode were utilized as complementary approaches. Subsequently, a series of sensitivity analyses were conducted to evaluate the robustness and reliability of the MR findings. Results: Our findings revealed that the IVW results indicated a significant increase in the prevalence of AD in individuals with genetically predicted CD (OR = 1.46, CI = 1.07-1.96, P _IVW = 0.014) and conversely (OR = 1.05, CI = 1.03-1.08, P _IVW = 4.80x10 ^-6 ). Furthermore, subsequent sensitivity analyses addressing heterogeneity, pleiotropy, and other potential biases substantiated these results. Conclusions: We established a bidirectional causal relationship between atopic dermatitis and celiac disease through a two-sample bidirectional MR study. Therefore, early screening and preventive measures are recommended for patients with atopic dermatitis and celiac disease to mitigate long-term complications and reduce additional burdens.