Causal relationships between autoimmune diseases and celiac disease: A Mendelian randomization analysis

Area of Science:

• Genetics and Epidemiology
• Immunology and Autoimmunity
• Gastroenterology

Background:

• Autoimmune disorders and celiac disease (CeD) share complex etiological pathways.
• Understanding the causal relationship between CeD and other autoimmune conditions is crucial for effective management and prevention strategies.
• Mendelian randomization (MR) offers a robust method to investigate potential causal links using genetic variants.

Purpose of the Study:

• To investigate the bidirectional causal relationship between celiac disease (CeD) and thirteen autoimmune diseases using Mendelian randomization (MR).
• To identify specific autoimmune diseases that causally influence the development of CeD.
• To determine if CeD causally increases the risk for developing other autoimmune conditions.

Main Methods:

• Utilized summary statistics from large-scale European genome-wide association studies (GWAS) for thirteen autoimmune diseases and celiac disease (CeD).
• Employed Inverse Variance-Weighted (IVW) method within a Mendelian randomization (MR) framework to assess genetic associations.
• Performed sensitivity analyses to ensure the reliability of results and rule out pleiotropy.

Main Results:

• Seven autoimmune diseases, including Crohn's disease (CD), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), and asthma, were found to be causally associated with CeD.
• Celiac disease (CeD) was identified as a causal risk factor for seven conditions: CD, Graves' disease (GD), PSC, psoriasis (PsO), SLE, T1D, and asthma.
• Sensitivity analyses confirmed the robustness of the findings, indicating no significant pleiotropic effects.

Conclusions:

• There is a significant bidirectional causal relationship between celiac disease (CeD) and multiple autoimmune disorders in the European population.
• CeD not only results from genetic predispositions shared with other autoimmune diseases but also actively contributes to their development.
• These findings underscore the interconnectedness of autoimmune conditions and highlight CeD as a potential upstream factor in the pathogenesis of several other autoimmune diseases.