Genetic link between primary biliary cholangitis and extrahepatic autoimmune diseases: A bidirectional two-sample Mendelian randomization study

Abstract

Abstract Background Observational studies have shown that patients with primary biliary cholangitis (PBC) have a higher incidence of extrahepatic autoimmune diseases (EHAIDs) than healthy individuals. However, whether this correlation is causal remains unclear. Methods Genetic instrumental variables associated with PBC and 7 EHAIDs were derived from published genome-wide association studies (GWAS) of European ancestry. A bidirectional two-sample Mendelian randomization (MR) analysis was used to determine the causal relationship between PBC and EHAIDs. Result We found that PBC can increase the susceptibility to type 1 diabetes (TD1), autoimmune hyperthyroidism (AITD), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), Psoriasis and Sarcoidosis with IVW odds ratio (OR) of 1.35 (95% CI: 1.28 ~ 1.43, p = 1.76×10 − 28), 1.19 (95% CI: 1.09 ~ 1.30, p = 0.00014),1.48 (95% CI: 1.36 ~ 1.61, p = 2.43×10 − 19), 1.13 (95% CI: 1.04 ~ 1.22, p = 0.0030), 1.09 (95% CI: 1.05 ~ 1.14, p = 4.50×10 − 5) and 1.11(95% CI: 1.03 ~ 1.19, p = 0.0064) respectively. Using reverse MR analysis, we also found that TD1 can increase the susceptibility to PBC, with IVW OR of 1.29 (95% CI: 1.19 ~ 1.41, p = 1.77×10 − 9). Conclusion PBC and TD1 may be causally related to each other. PBC can increase the susceptibility to AITD, SLE, AS, Psoriasis and Sarcoidosis. It reminds us that we should pay attention to screening for these EHAIDs in clinical PBC patients to improve the patient's survival rate and quality of life.