Abstract
Background: Primary biliary cholangitis (PBC) is an autoimmune disease and is often accompanied by thyroid dysfunction. Understanding the potential causal relationship between PBC and thyroid dysfunction is helpful to explore the pathogenesis of PBC and to develop strategies for the prevention and treatment of PBC and its complications. Methods: We used a two-sample Mendelian randomization (MR) method to estimate the potential causal effect of PBC on the risk of autoimmune thyroid disease (AITD), thyroid-stimulating hormone (TSH) and free thyroxine (FT4), hyperthyroidism, hypothyroidism, and thyroid cancer (TC) in the European population. We collected seven datasets of PBC and related traits to perform a series MR analysis and performed extensive sensitivity analyses to ensure the reliability of our results. Results: Using a sensitivity analysis, we found that PBC was a risk factor for AITD, TSH, hypothyroidism, and TC with odds ratio (OR) of 1.002 (95% CI: 1.000–1.005, p = 0.042), 1.016 (95% CI: 1.006–1.027, p = 0.002), 1.068 (95% CI: 1.022–1.115, p = 0.003), and 1.106 (95% CI: 1.019–1.120, p = 0.042), respectively. Interestingly, using reverse-direction MR analysis, we also found that AITD had a significant potential causal association with PBC with an OR of 0.021 (p = 5.10E−4) and that the other two had no significant causal relation on PBC. Conclusion: PBC causes thyroid dysfunction, specifically as AITD, mild hypothyroidism, and TC. The potential causal relationship between PBC and thyroid dysfunction provides a new direction for the etiology of PBC.
Highlights
Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease with a progressive disease (Lleo et al, 2017)
Based on IVW, we found that TSH, hypothyroidism, and TC were heterogeneous as compared with AITD, FT4, and hypothyroidism
We used the result from the fixed-effects IVW method to represent the causal effect of PBC on AITD; the result from fixed-effects IVW method with outlier excluded was used to represent the causal effect of PBC on TSH; and the result from fixed-effects IVW method with outlier excluded was used to represent the causal effect of PBC on hypothyroidism
Summary
Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease with a progressive disease (Lleo et al, 2017). Some population-based studies that investigate the incidence and prevalence of PBC are increasing year by year (Carey et al, 2015; Rosa et al, 2018; Lindor et al, 2019). With increasing prevalence and serious complications, it is worthy of our further study to explore the possible pathogenesis of PBC. Primary biliary cholangitis (PBC) is an autoimmune disease and is often accompanied by thyroid dysfunction. Understanding the potential causal relationship between PBC and thyroid dysfunction is helpful to explore the pathogenesis of PBC and to develop strategies for the prevention and treatment of PBC and its complications
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
