The association among multiple-site chronic pain, sedentary behavior, and major depressive disorders: a mendelian randomization study.

Objective: Observational studies have reported that major depressive disorder (MDD) is associated with sedentary behavior (SB) and multiple chronic pain (MCP), but their associations remain unclear. Mendelian randomization analysis was used to assess the association.

Methods: Single nucleotide polymorphisms (SNPs) associated with MCP, SB [time spent watching television (Tel), using a computer (Com), or driving (Dri)], and MDD were collected from genome-wide association studies and screened as instrumental variants with a threshold of 1 × 10 -5 . Mendelian randomization was performed to examine their associations. Sensitivity analyses were conducted to evaluate robustness.

Results: MCP was associated with a higher risk of MDD [odds ratio (OR) inverse variance weighting (IVW)  = 1.88; 95% confidence interval (CI), 1.64-2.15; P  = 4.26 × 10 -8 ), and causally related to SB (Tel: OR IVW  = 1.23; 95% CI, 1.19-1.26; P  = 6.02 × 10 -38 ) (Dri: OR IVW  = 1.05; 95% CI, 1.03-1.08; P  = 3.92 × 10 -5 ). Causality of SB on MCP was detected for Tel (OR IVW  = 1.46; 95% CI, 1.39-1.53; P  = 1.40 × 10 -54 ) and Com (OR IVW  = 0.88; 95% CI, 0.83-0.93; P  = 2.50 × 10 -6 ). No association was observed for SB on MDD. There is currently insufficient evidence to support that leisure activities are a mediating factor in MCP-induced MDD.

Conclusion: There are complex relationships among MCP, SB, and MDD. More research and learning about potential relationships and mechanisms among these phenotypes should be supplied.