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

Area of Science:

• Genetics
• Epidemiology
• Psychiatry

Background:

• Observational studies suggest a link between depression and musculoskeletal disorders (MSDs).
• The causal relationship between depression and specific MSDs remains poorly understood.
• Mendelian randomization (MR) offers a method to investigate bidirectional causal effects.

Purpose of the Study:

• To investigate the bidirectional causal relationships between depression and specific MSDs.
• Utilize Mendelian randomization (MR) to explore genetic predispositions.
• Examine associations in both European and East Asian populations.

Main Methods:

• Employed bidirectional Mendelian randomization (MR) using genome-wide association study (GWAS) data.
• Utilized independent single nucleotide polymorphisms (SNPs) as instrumental variables (IVs).
• Applied various estimation methods (IVW, MR-RAPS) and sensitivity analyses (MR-PRESSO) to assess robustness and detect pleiotropy/heterogeneity.

Main Results:

• Genetically predicted depression was associated with increased risk of neck-shoulder pain (OR 1.48), hip pain (OR 1.20), and knee pain (OR 1.29).
• Reverse MR indicated significant effects of neck-shoulder pain (OR 1.08), back pain (OR 1.00), hip pain (OR 1.06), and knee pain (OR 1.02) on depression risk.
• Most analyses showed no significant heterogeneity or horizontal pleiotropy, though some reverse analyses indicated potential violations.

Conclusions:

• Genetic predisposition to depression is linked to a higher risk of neck-shoulder, hip, and knee pain.
• Conversely, neck-shoulder, back, hip, and knee pain show reverse associations with depression risk.
• These preliminary findings warrant further clinical validation to confirm the bidirectional causal links.