Leptin in Relation to Degenerative orthopaedic diseases: A Two-Sample Mendelian Randomization Study

Abstract Background: We conducted a mendelian randomization study to assess the relationship between serum leptin levels and three degenerative orthopaedic diseases. Methods: From genome-wide association studies of European ancestry, we selected instrumental variables for leptin(p<5×10–6). Meanwhile, we retrieved the summary statistics of three degenerative orthopaedic diseases as outcomes. We performed IVW, Weighted median and MR-Egger method analysis. To avoid heterogeneity and pleiotropy,we also performed sensitivity analysis. Results: Overall, the results showed a causal relationship between leptin and the development of osteoporosis.We found a causal relationship between serum leptin levels and the development of osteoporosis mainly based on the results of the inverse variance weighting method(p=0.028).Contrarily, leptin was not found to be causally related to the occurrence of knee osteoarthritis(p=0.531), lumbar disc herniation(p=0.931).Sensitivity analyses suggested the robustness of MR results, which were less likely to be biased by unbalanced pleiotropy orevident heterogeneity. Conclusion: We found a causal relationship between leptin and osteoporosis. However, there was no such relationship with knee osteoarthritis and lumbar disc herniation. Keywords：degenerative orthopaedic diseases, leptin, mendelian randomization, genome-wide association study, cause-and-effect relationship