Two-sample Mendelian randomization analysis of the causal association between circulating inflammatory proteins and osteosarcoma

Objective: To investigate the causal relationship between 91 circulating inflammatory proteins and osteosarcoma using the two-sample Mendelian randomization method. Method: Corresponding exposure and outcome data were extracted from genome-wide association study (GWAS) databases. A two-sample Mendelian randomization analysis was conducted on the data, with the inverse-variance weighted (IVW) method serving as the primary analytical approach. This was complemented by MR-Egger, weighted median, simple mode, and weighted mode methods to validate the results. Sensitivity analyses were also performed to verify the reliability of the data. Results: The IVW analysis revealed a positive causal relationship between GCST90274776 (OR = 3.02, 95% CI: 0.033–0.117, P = 0.028), GCST90274822 (OR = 1.603, 95% CI: 1.014–2.535, P = 0.043), and GCST90274847 (OR = 2.580, 95% CI: 1.155–5.762, P = 0.021) and osteosarcoma. In contrast, GCST90274844 (OR = 0.313, 95% CI: 0.155–0.634, P = 0.001) showed a negative causal relationship with osteosarcoma. The supplementary analysis methods (MR-Egger, weighted median, simple mode, and weighted mode) consistently validated the direction and magnitude of these findings. The sensitivity analysis indicated that the data were reliable and free from bias. Conclusion: Using the Mendelian randomization approach, this study suggest that GCST90274776, GCST90274822, and GCST90274847 may be risk factors for osteosarcoma, whereas GCST90274844 appears to exhibit a protective effect against the disease.