Biopsychosocial science and medicine · 2026
Exploring Causal Correlations Between Depression and Musculoskeletal Disorders: A Bidirectional Mendelian Randomization Study.
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Tong Jingyi, Zhu Min, Tan Weijia, Chen Jiajia
Аннотация
OBJECTIVE: 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).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.