Posttraumatic stress disorder is a risk factor for migraine: two-sample Mendelian randomization and bioinformatic analysis

Abstract

Background The association between posttraumatic stress disorder (PTSD) and migraine is a matter of particular concern in clinical practice. Migraine can manifest as the initial somatic symptom of PTSD, one of its sequelae, or even serve as a significant obstacle to effectively treating PTSD. Additionally, individuals with migraines are more susceptible to developing PTSD. Consequently, this study employed bidirectional Mendelian randomization (MR) analysis to investigate the causal relationship between PTSD and migraine while utilizing bioinformatics to analyze their mechanistic connection. Methods We identified single-nucleotide polymorphisms (SNPs) associated with migraine and PTSD through genome-wide association studies (GWASs) conducted by independent consortia. Then, we used these SNPs as instrumental variables to estimate the causal effects of migraine on PTSD and vice versa. MR analysis was performed using the inverse-variance weighted (IVW) method. The MR‒Egger method and the weighted median method were employed to assess the robustness of the findings. Additionally, disease targets associated with both PSTD and migraine were identified by searching the DisGeNET and OMIM databases. The Venny 2.1 software tool was utilized to determine the intersections among these targets, which were then imported into the STRING database for constructing a PPI network. Subsequently, the Cytoscape 3.7 software tool was used for visualization and analysis of the network. Furthermore, common targets were imported into Metascape for Gene Ontology (GO) and KEGG pathway enrichment analysis. Results MR analysis revealed a substantial causal association between PTSD and migraine;however, currently, there is no definitive causal link established between aura migraines or nonaura migraines and PTSD. A total of 107 targets were found to be common to both PTSD and migraine patients. Subsequently, a PPI network comprising 92 nodes connected by 845 edges was constructed based on these shared disease targets. Enrichment analysis revealed their involvement in various BPs, CCs, and MFs. Additionally, the analysis indicated their association with 12 KEGG signaling pathways. Conclusion These results revealed a causal relationship between PTSD and migraine and suggested that further investigations into the mechanisms and specific targets involved in PTSD and migraine should focus particularly on aspects such as neurodegenerative changes, inflammation and the CAMP pathway.