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

Abstract

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.