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Primary biliary cholangitis has causal effects on systemic rheumatic diseases: a Mendelian randomization study.

Hai-Ping Zhang1, Zhe Zhou2, Ke Chen1

  • 1Department of Gastroenterology, Hubei NO. 3 People's Hospital of Jianghan University, Wuhan, 430000, China.

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|August 29, 2024
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Summary

This study used Mendelian randomization to investigate the causal link between primary biliary cholangitis (PBC) and systemic rheumatic diseases (SRDs). PBC was found to have causal effects on several SRDs, offering new insights into their relationship.

Keywords:
Mendelian randomizationPrimary biliary cholangitisSystemic rheumatic diseases

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Area of Science:

  • Immunology
  • Genetics
  • Rheumatology

Background:

  • Observational studies suggest an association between primary biliary cholangitis (PBC) and systemic rheumatic diseases (SRDs).
  • The precise causal relationship between PBC and SRDs remains unclear.
  • Mendelian randomization (MR) offers a robust method to investigate causality.

Purpose of the Study:

  • To evaluate the potential causal effects of primary biliary cholangitis (PBC) on various systemic rheumatic diseases (SRDs).
  • To leverage genetic variants associated with PBC as instrumental variables in a Mendelian randomization analysis.
  • To elucidate the etiological link between PBC and conditions like Sjögren syndrome, rheumatoid arthritis, and others.

Main Methods:

  • Genome-wide association study (GWAS) summary data were utilized from open-access databases.
  • Independent genetic variants for PBC were identified and used as instrumental variables.
  • Inverse variance weighted (IVW) method was the primary analytical approach, with MR-Egger and Cochran's Q tests for pleiotropy and heterogeneity assessment.

Main Results:

  • Primary biliary cholangitis (PBC) demonstrated statistically significant causal effects on Sjögren syndrome (SS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), mixed connective tissue disease (MCTD), and polymyositis (PM).
  • Odds ratios (ORs) ranged from 1.071 for RA to 1.447 for SLE, with all P-values < 0.001, indicating strong associations.
  • Absence of significant horizontal pleiotropy (MR-Egger P > 0.05) and heterogeneity confirmed the robustness of the findings.

Conclusions:

  • This Mendelian randomization study provides compelling evidence for a causal relationship between primary biliary cholangitis (PBC) and multiple systemic rheumatic diseases (SRDs).
  • The findings suggest that PBC may contribute to the development or progression of these rheumatic conditions.
  • These results offer novel insights into the complex interplay between autoimmune liver and systemic autoimmune diseases.