To determine the causal relationship between multisite chronic pain (MCP) and post-traumatic stress disorder (PTSD) using Mendelian Randomization (MR) analysis. Genome-wide summary statistics for MCP and PTSD were obtained. Linkage disequilibrium score regression (LDSC) analysis was used to assess genetic correlation. Independent SNPs associated with MCP and PTSD were used as instrumental variables for forward and reverse MR analyses. The inverse variance weighted (IVW) method was the primary analysis, with additional sensitivity tests to ensure robustness. LDSC identified a significant genetic correlation between MCP and PTSD (rg = 0.635, P = 1.40E-110). The forward MR analysis indicated a positive causal association between the number of MCP sites and the PTSD risk (Odds Ratio [OR] = 1.103, 95% CI: 1.026-1.186, P = 7.89E-03). Conversely, the reverse MR analysis showed that PTSD significantly increased the number of MCP sites (β = 0.244, 95% CI: 0.143-0.345, P = 2.08E-06). Sensitivity tests suggested the robustness of the MR estimation, indicating no significant heterogeneity or horizontal pleiotropy. A bidirectional positive causal relationship between MCP and PTSD was identified, highlighting the need for integrated treatment and preventive strategies that address both conditions simultaneously to improve health outcomes.
Keywords: Causal inference; Mendelian randomization analysis; Multisite chronic pain; Post-traumatic stress disorder; Risk factors.
© 2025. The Author(s).