Causal Relationship Between Systemic Lupus Erythematosus and Osteoporosis: A Mendelian Randomization Analysis

Background: Systemic Lupus Erythematosus (SLE) and Osteoporosis are two prevalent medical conditions. Previous studies have suggested a possible correlation between SLE and osteoporosis, though the underpinning causal relationship remains largely unknown. The current study aimed to elucidate the causal association between SLE and osteoporosis by employing a Mendelian randomization (MR) approach. Methods We performed two-sample MR analysis using the inverse variance-weighted (IVW), weighted median, and MR-Egger methods on publicly available summary statistics datasets using a SLE genome-wide association study (GWAS) as an exposure and osteoporosis GWASs in people with East Asia ancestry as outcomes. The pleiotropy and heterogeneity were examined using a variety of techniques, including the MR-Egger intercept, the MR-PRESSO approach, and the Cochran’s Q test. Results We selected 74 single-nucleotide polymorphisms from a SLE GWAS as instrumental variables for osteoporosis. The IVW ( p  < 0.05) and weighted median ( p  < 0.05) method results support a causal association between SLE and osteoporosis. MR-Egger intercept (p = 0.3474) and MR-PRESSO global test (p = 0.3285) did not suggest evidence of horizontal or directional pleiotropy. Cochran’s Q test (p = 0.3027) showed that there was no heterogeneity between IVs. Conclusion This MR analysis provides insight into the potential causal relationship between SLE and osteoporosis, emphasizing the potential contribution of SLE-associated genetic variants to osteoporosis risk.