Genetic link between celiac disease and autoimmune liver diseases: A two-sample Mendelian randomization study

Abstract Objective: Although previous epidemiological studies have reported an association between Celiac disease (CeD) and Autoimmune liver disease (AILD), the causal relationship between them remains unclear. This study aimed to assess the bidirectional causal relationship between CeD and AILD using Mendelian randomization (MR). Methods: We obtained genome-wide association study (GWAS) datasets of CeD, PBC and PSC of thoroughly European ancestry from the IEU GWAS database and GWAS of AIH from GWAS Catalog. MR analyses were performed with inverse variance weighted (IVW), MR-Egger and weighted median methods. Results: Positive causal effects of genetic predisposition to CeD on PSC (IVW OR = 1.16, 95% CI = 1.04-1.29, p = 0.0095) and AIH (IVW OR = 1.09, 95% CI = 1.02-1.17, p = 0.0126) were derived, with no causal effect on PBC. The results of reverse MR analysis demonstrated that genetic susceptibility to PBC was associated with an increased risk of CeD (IVW OR = 1.09, 95% CI = 1.01-1.17, p = 0.0267). Conclusion: This study reveals a causality of CeD on PSC and AIH and PBC on CeD among patients of European descent. It differs slightly from previous observational studies, suggesting that the mechanisms of interaction between AILD and CeD needs further exploration.