Exploring the association between systemic lupus erythematosus and osteonecrosis by Mendelian randomization analysis

Area of Science:

• Genetics
• Rheumatology
• Epidemiology

Background:

• Systemic lupus erythematosus (SLE) patients exhibit a high risk of osteonecrosis.
• The genetic basis connecting SLE, gout, rheumatoid arthritis, and osteonecrosis remains unclear.
• Understanding these genetic links is crucial for elucidating osteonecrosis mechanisms.

Purpose of the Study:

• To investigate the potential causal relationships between SLE, gout, rheumatoid arthritis, and osteonecrosis using genetic data.
• To perform post-Genome-Wide Association Studies (GWAS) localization and functional analyses for osteonecrosis-related GWAS.
• To deepen the understanding of osteonecrosis pathogenesis through genetic susceptibility studies.

Main Methods:

• Utilized two-sample Mendelian randomization (MR) analysis with inverse-variance weighting (IVW), MR-Egger, and weighted median methods.
• Selected 45 single nucleotide polymorphisms (SNPs) associated with SLE from public GWAS datasets.
• Conducted sensitivity analyses using Cochrane Q-test, MR-Egger interception, and other methods to ensure result validity.

Main Results:

• No significant causal effect was found between SLE and osteonecrosis.
• Multi-phenotype MR analysis indicated no significant causal effect between gout or rheumatoid arthritis and osteonecrosis.
• Heterogeneity analyses showed no significant differences between instrumental variables (P > 0.05).

Conclusions:

• Current evidence does not support a significant causal effect of gout or rheumatoid arthritis on osteonecrosis risk.
• While the IVW method suggested a potential link between SLE and osteonecrosis, the evidence validity is insufficient.
• The study provides a theoretical basis for further research into SLE heritability and its connection to osteonecrosis.