OBJECTIVE: We conducted a meta-analysis and Mendelian randomization study to analyze the association and causal relationship of genetic prediction between post-traumatic stress disorder and the risk of systemic lupus erythematosus. METHODS: A meta-analysis was conducted using hazard ratio, relative risk, odds ratio, and 95 % confidence intervals as effect measures. Summary data from genome-wide association studies on post-traumatic stress disorder and systemic lupus erythematosus were utilized to assess the causal relationship of genetic prediction between post-traumatic stress disorder and systemic lupus erythematosus using Mendelian randomization. RESULTS: A meta-analysis showed that post-traumatic stress disorder was positively associated with the risk of systemic lupus erythematosus (RR = 1.85, 95 % CI = 1.61-2.12, p <
0.002). The results of Egger's test showed no publication bias (p = 0.823, p >
0.05). Sensitivity analysis showed that the meta-analysis results were stable (RR = 1.85, 95 % CI = 1.61-2.12). However, Mendelian Randomization analysis revealed no evidence of a causal relationship of genetic prediction between post-traumatic stress disorder and systemic lupus erythematosus (IVW OR: 1.002, 95 % CI: 0.805-1.245, p = 0.993). CONCLUSION: There is a correlation between post-traumatic stress disorder and systemic lupus erythematosus, but Mendelian Randomization does not support a genetic causal effect of post-traumatic stress disorder on systemic lupus erythematosus. The potential causal relationship between the two factors may necessitate further in-depth research.