Causal association between depression and myalgia-related disorders: A bidirectional mendelian randomization study.

OBJECTIVE

The connection between depression and myalgia-related disorders remains unclear. We investigated the bidirectional causal relationship between depression and five such disorders using Mendelian randomization (MR).

METHOD: Genetic instrumental variables for depression were obtained from a GWAS of 170,756 individuals with depression and 329,443 controls. The primary two-sample MR analysis used the inverse variance-weighted (IVW) method. Robustness was tested with MR Egger, weighted median, and weighted mode approaches. We also conducted heterogeneity, pleiotropy, and sensitivity analyses to ensure result reliability.

RESULTS

Depression showed significant positive associations with myalgia [IVW, OR = 1.468, 95 % CI: 1.246-1.729, P = 4.19 × 10-6], fibromyalgia [OR = 2.328, 95 % CI: 1.771-3.061, P = 1.39 × 10-9], and osteoarthritis [OR = 1.242, 95 % CI: 1.147-1.345, P = 9.58 × 10-8]. No causal association was found with myositis or rheumatoid arthritis (P > 0.05). In reverse MR, osteoarthritis showed a significant association with depression [OR = 1.113, 95 % CI: 1.025-1.210, P = 0.011], while other disorders did not (P > 0.05).

CONCLUSION

Our findings suggest a genetic causal relationship between depression and increased risk of myalgia, fibromyalgia, and osteoarthritis. Moreover, osteoarthritis may increase depression risk, supporting a potential bidirectional link. These results underscore the importance of timely depression management to mitigate risks of myalgia-related conditions.