Causal relationship between primary biliary cholangitis on osteoporosis: A two-sample Mendelian randomization study

Abstract

This present study aims to investigate the relationship between primary biliary cholangitis (PBC) and osteoporosis (OP) using a two-sample Mendelian randomization (MR) analysis. A two-sample MR study was conducted to explore the association between PBC and OP. The inverse variance weighted test was primarily used to estimate causality. Horizontal pleiotropy was assessed using both MR-PRESSO and MR-Egger regression techniques. Cochran Q test was applied to examine heterogeneity among single nucleotide polymorphisms (SNPs), and a sensitivity analysis was performed to evaluate the impact of each individual SNP on the MR analysis results. The two-sample MR analysis result showed a significant association between PBC and OP, with an inverse variance weighted odds ratio of 1.098 (95% confidence interval: 1.049-1.150,and a P = 5.41e-05). MR-Egger regression indicated no bias due to genetic pleiotropy (intercept = 0.007, SE = 0.022, P = .754). Cochran Q test revealed no significant heterogeneity (Q = 27.494, P = .236). Furthermore, leave-one-out analysis confirmed the robustness of our findings, as the results remained consistent even when individual SNPs were excluded. This study provides evidence supporting the notion that PBC may increase the risk of OP, enhancing our understanding of the association between PBC and OP.

Keywords: Mendelian randomization; OP; PBC; causal inference.

Figure 1.

The study design examines the causal link between PBC and OP using MR, with 3 key assumptions. OP = osteoporosis, PBC = primary biliary cholangitis.

Figure 2.

Forest plot illustrating the impact of PBC on the risk of OP. IVW = inverse variance weighted, MR = Mendelian randomization, OP = osteoporosis, PBC = primary biliary cholangitis.

Figure 3.

Scatter plot demonstrating the impact of PBC on the risk of developing OP. The slope of the linear line indicates the strength of the cause-and-effect relationship. IVW = inverse variance weighted, MR = Mendelian randomization, OP = osteoporosis, PBC = primary biliary cholangitis.

Figure 4.

Funnel plots were used to visualize the overall heterogeneity of MR estimates regarding the effect of PBC on total OP. IVW = inverse variance weighted, MR = Mendelian randomization, OP = osteoporosis, PBC = primary biliary cholangitis.

Figure 5.

A leave-one-out plot was used to visualize the causal effect of PBC on total OP risk when excluding 1 SNP at a time. MR = Mendelian randomization, OP = osteoporosis, PBC = primary biliary cholangitis, SNPs = single nucleotide polymorphisms.