Causal relationship between primary biliary cholangitis and inflammatory bowel disease: a Mendelian randomization study

Background: Several studies indicated that inflammatory bowel disease (IBD) may contribute to increased susceptibility to primary biliary cholangitis (PBC). However, the causal relationship between IBD and PBC remains unclear.

Methods: The genetic variant data of patients with IBD and PBC were obtained from published genome-wide association studies (GWASs). The IBD data were further divided into a discovery dataset and a validation dataset depending on the data source. We conducted a two-sample Mendelian randomization (MR) analysis using the inverse variance weighting (IVW), MR-Egger, weighted median (WM), MR robust adjusted profile score (MR-RAPS), and maximum likelihood (ML) methods, with IVW being the main focus, to verify the causal relationship between IBD and PBC. Additionally, a series of sensitivity analyses were performed to ensure the reliability of the results.

Results: In the discovery cohort, the IVW analysis results (OR = 1.114, P = 0.011) indicated a significant association between IBD and PBC. The MR-RAPS (OR = 1.130, P = 0.007) and ML (OR = 1.115, P = 0.011) analyses yielded results consistent with those of IVW in confirming IBD as a risk factor for PBC. In the validation cohort, consistent findings were observed regarding the causal relationship between IBD and PBC using IVW, MR-RAPS, and ML analyses; all three methods identified IBD as a risk factor for developing PBC. By the IVW analysis, Crohn's disease (CD) emerged as the most prominent subtype of IBD associated with an increased risk of developing PBC in both the discovery cohort (OR = 1.068, P = 0.049) and the validation cohort (OR = 1.082, P = 0.019).

Conclusion: The results of the MR analysis suggest a causal relationship between IBD and PBC, highlighting the necessity for proactive PBC prevention in patients with IBD, particularly those with CD.