Exploring Causal Correlations Between Depression and Musculoskeletal Disorders: A Bidirectional Mendelian...

Observational studies suggest a strong but poorly understood association between depression and musculoskeletal disorders (MSDs). This study aims to investigate the bidirectional causal relationships between depression and specific MSDs using Mendelian randomization (MR).

Bidirectional MR used GWAS data from European (n=484,598) and East Asian (n=152,389) populations. Independent SNPs ( p <5×10 - ⁸; supplementary p <1×10 - ⁷; F>10) were IVs. Causal effects were estimated via inverse variance weighted (IVW), MR-RAPS, and other methods, with sensitivity tests (MR-PRESSO, stratified analysis) for pleiotropy/heterogeneity.

Genetically predicted depression was associated with increased risk of neck-shoulder pain (IVW OR 1.48, 95% CI 1.26-1.71, p =7.14×10 - ⁶), hip pain (OR 1.20, 95% CI = 1.05-1.37, p =.005), and knee pain (OR 1.29, 95% CI = 1.09-1.52, p =.002), but not back or low back pain. Reverse MR indicated significant effects of neck-shoulder pain (OR 1.08, 95% CI = 1.05-1.12, p =6.22×10 - ⁷), back pain (OR 1.00, 95% CI = 0.99-1.00, p =1.18×10 - ¹¹), hip pain (OR 1.06, 95% CI = 1.01-1.12, p =.014), and knee pain (OR 1.02, 95% CI = 1.00-1.05, p =.025) on depression risk. No significant heterogeneity or horizontal pleiotropy was detected in most analyses, though some reverse analyses showed evidence of these violations.

Genetic prediction of depression correlates with increased neck-shoulder/hip/knee pain risk, with reverse associations for these MSDs and depression. Findings are preliminary and require clinical validation.