Association between diabetes mellitus and primary biliary cholangitis: a two-sample Mendelian randomization study

Area of Science:

• Genetics and Epidemiology
• Gastroenterology and Endocrinology

Background:

• Observational studies suggest a link between diabetes mellitus (DM) and primary biliary cholangitis (PBC).
• The causal relationship and directionality between DM and PBC remain unclear, necessitating further investigation.

Purpose of the Study:

• To investigate the potential causal associations between diabetes mellitus (DM) and primary biliary cholangitis (PBC).
• To determine the directionality of any identified causal links between DM subtypes and PBC.

Main Methods:

• Utilized genome-wide association study (GWAS) datasets for PBC, Type 1 diabetes (T1DM), and Type 2 diabetes (T2DM).
• Employed various Mendelian randomization (MR) methods, including Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median (WM).
• Conducted sensitivity analyses and reverse MR analyses to ensure the robustness and directionality of causal inferences.

Main Results:

• A significant causal effect of T1DM on increasing the risk of PBC was observed (IVW: OR 1.1525, p = 0.0007).
• Reverse MR analysis indicated that PBC is associated with an increased risk of T1DM (IVW: OR 1.1991, p = 1.81E-07).
• No significant causal relationship was found between Type 2 diabetes (T2DM) and PBC in either direction.

Conclusions:

• The study provides evidence for a bidirectional causal relationship between Type 1 diabetes and primary biliary cholangitis.
• No causal link was established between Type 2 diabetes and primary biliary cholangitis.
• Further validation in larger populations is recommended to confirm these findings.