The mediating role of depression in Gastroesophageal Reflux Disease (GERD) and migraine

The study used data from genome-wide association studies (GWAS) to conduct two-sample bidirectional RM analyses. This approach allowed causality to be tested in both directions: from GERD to migraine and vice versa. Multivariate MR analysis was performed to adjust for potential confounders such as smoking, alcohol consumption, obesity, type 2 diabetes and depression. MR mediation analysis was used to assess the role of depression in the relationship between GERD and migraine.

The main methods used included the inverse variance weighted (IVW) method, as well as sensitivity methods such as MR-Egger, weighted median and leave-one-out analysis. Heterogeneity and pleiotropy were assessed to ensure the reliability of the results.

The two-way RM analysis revealed a positive causal effect of GERD on migraine, indicating that people with GERD have an increased risk of developing migraines. In contrast, migraine does not increase the risk of GERD. Multivariable MR analysis confirmed that the positive causal effect of GERD on migraine persisted after adjustment for confounders. The MR mediation analysis revealed that depression mediated 28.72% of the effect of GERD on migraine, highlighting the importance of depression as an intermediary factor in this relationship.

The results of this study clarified the positive causal effect of GERD on migraine risk, while highlighting the significant mediating role of depression. This suggests that effective management of GERD, particularly through interventions targeting depression, could help prevent migraine. These findings have important clinical implications, indicating that treatments aimed at controlling GERD and reducing depression could reduce the prevalence and severity of migraines.

The authors call for future research to further explore the specific pathophysiological mechanisms by which GERD influences migraine risk. Such studies could facilitate the development of more effective pharmacological targets or disease management strategies to reduce the impact of GERD and migraine on patients' quality of life.