Celiac Disease as a Genetic Predisposing Factor for Dermatitis Herpetiformis: A Two-Sample Mendelian Randomization Analysis

Yani Su,1,* Peng Xu,2,* Ming Zhang,3,* Pengfei Wen,2 Ke Xu,2 Jiale Xie,2 Xianjie Wan,2 Lin Liu,2 Zhi Yang,2 Mingyi Yang2 1Department of Radiotherapy, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Joint Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Department of General Practice, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingyi Yang, Email [email protected] Zhi Yang, Email [email protected]: Observational studies have consistently highlighted a robust clinical association between celiac disease (CD) and dermatitis herpetiformis (DH). Building on this foundation, the present study aims to investigate whether this observed relationship is underpinned by a causal genetic mechanism, providing insights into the potential hereditary basis of their connection.Methods: This study employed bidirectional two-sample Mendelian randomization (MR) analysis to investigate the potential genetic causality between CD and DH, utilizing genome-wide association study (GWAS) summary data. To comprehensively examine the genetic relationship between CD and DH, we applied multiple MR methodologies. Furthermore, to enhance the robustness and credibility of our results, we conducted extensive sensitivity analyses.Results: The fixed-effects inverse variance weighted (IVW) analysis revealed a significant positive genetic causal relationship between CD and DH (P = 0.001, odds ratio [OR] 95% confidence interval [CI]: 1.546 [1.195– 1.999]). In contrast, no significant genetic causality was found in the reverse direction, from DH to CD (P = 0.113, OR 95% CI: 1.039 [0.991– 1.090]). Notably, the MR analysis revealed no evidence of heterogeneity, further reinforcing the reliability of the fixed-effects IVW model. Additionally, sensitivity analyses confirmed the stability and robustness of the results, further validating the integrity of the conclusions drawn from the MR analysis.Conclusion: The results of our study indicate that CD acts as a genetic susceptibility factor for the development of DH. Furthermore, the occurrence of DH in individuals with a history of CD appears to be attributed to a causal genetic relationship, suggesting that the genetic predisposition linked to CD may drive the manifestation of DH.Keywords: celiac disease, dermatitis herpetiformis, mendelian randomization, causal, genetic