Associations between post-traumatic stress disorder and neurological disorders: A genetic correlation and Mendelian randomization study

Observational studies have reported a close relationship between post-traumatic stress disorder (PTSD) and neurological disorders, but the existence of a causal link remains uncertain. The aim of this study is to investigate these relationships and potential mediators via Mendelian randomization (MR) analysis. We sourced pooled data for genome-wide association study (GWAS) of PTSD (n = 1,222,882) from the psychiatric genomics consortium. Summary-level data for eight neurological traits were derived from large-scale GWASs. Genetic correlations were computed using linkage disequilibrium (LD) score regression. The inverse variance weighted (IVW) method served as the primary analysis method for MR. We employed a range of sensitivity analysis methods to ensure result robustness. A two-step approach was utilized to ascertain the effects and proportions of mediations. We identified significant genetic associations between PTSD and any dementia, cognitive performance, multiple sclerosis, and migraine. MR analysis revealed a significant association between PTSD and an increased risk of migraine (P = 0.02). This was substantiated by the results of several sensitivity analyses. Notably, the robust association between PTSD and migraine persisted even after adjustment for major depressive disorder and anxiety. Mediation analysis revealed that both alcohol intake frequency and insomnia partially mediated the association between PTSD and migraine. Participants in the MR analysis were of European descent, and verification in other ethnicities was not possible due to data limitations. Our findings indicate a close association between PTSD and migraine. Alcohol intake frequency and insomnia serve as intermediate factors, partially explaining the relationship between PTSD and migraine.