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

Patients with systemic lupus erythematosus (SLE) have been shown to have a high risk of osteonecrosis, but the potential causal relationship between genetic susceptibility and risk of osteonecrosis is unclear. In this study, we used Mendelian randomization to investigate the effects of SLE, gout and rheumatoid arthritis on osteonecrosis, and performed post-GWAS localization and functional analyses of GWAS studies related to osteonecrosis, with the aim of obtaining a more in-depth understanding of the mechanisms of osteonecrosis. In this study, a total of 45 single nucleotide polymorphisms (SNPS) data associated with SLE from publicly available genome-wide association study (GIS) datasets were selected for magnetic resonance estimation using inverse-variance weighting, MR-Eagle method and weighted median method. The Cochrane Q-test, MR-Egger interception, MR-multidirectional residual and outlier methods, entrance/exit analysis and funnel plot were applied for sensitivity analysis. Two-sample Mendelian randomization analysis of the 19 SNPs obtained from screening showed no significant causal effect of SLE and osteonecrosis, and IVW and MR-Egger heterogeneity analyses showed no significant heterogeneity between the instrumental variables (P > 0.05). Multi-phenotype MR analysis showed no significant causal effect between gout and rheumatoid arthritis and osteonecrosis (p > 0.05). The available evidence does not support a significant causal effect of gout and rheumatoid arthritis on osteonecrosis, and the causal effect of SLE on the increased risk of osteonecrosis is only supported by the IVW method, which is of insufficient evidence validity, but suggests a better theoretical basis for the study of heritability related to SLE.