Analysis of the causal association between systemic lupus erythematosus and osteonecrosis: A bidirectional 2-sample Mendelian randomization study

Abstract

Previous studies have indicated that multisite osteonecrosis (ON), particularly femoral head necrosis, is a common and serious complication of systemic lupus erythematosus (SLE). However, the pathogenesis of ON in patients with SLE is unclear and existence of a causal relationship between SLE and ON remains uncertain. Therefore, using summary-level data from large-scale genome-wide association studies of European individuals, we designed a bidirectional 2-sample Mendelian randomization (MR) analysis to comprehensively assess the genetic association between SLE and ON. Data on SLE and osteonecrosis were obtained from genome-wide association studies. In addition, we used multiple analytical methods, including MR-Egger, weighted mode, simple mode, and weighted median, to strengthen the final results. Furthermore, several sensitivity analyses were performed to ensure the validity and robustness of the results. The initial and validation MR analyses indicated that genetically predicted SLE had no effect on the risk of ON (odds ratio = 1.02, 95% confidence interval = 0.952-1.093, P = .568). Likewise, the reverse MR analysis did not find substantial support for a significant association between ON and SLE (odds ratio = 1.044, 95% confidence interval = 0.906-1.203, P = .0553). Supplementary MR methods and sensitivity analyses provided additional confirmation of the reliability of the MR results. The results of the "Leave-one-out" analysis indicated that our MR conclusions were not driven by any single SNP. Although our bidirectional dual sample MR analysis did not find any genetic evidence supporting a significant association between SLE and ON, our study a certain extent contributed to understanding the pathogenesis of SLE combined with ON.

Keywords: Mendelian randomization; causal association; osteonecrosis; systemic lupus erythematosus.