Bidirectional analysis of gastroesophageal reflux disease and migraine using two-sample Mendelian randomization

Background Epidemiological studies suggest a link between gastroesophageal reflux disease (GERD) and migraine, but the causal relationship remains unclear. This study aimed to clarify this relationship using two-sample Mendelian Randomization (MR). Methods Data on GERD and migraine, including subtypes with aura (MA) and without aura (MO), were collected from genome-wide association studies (GWAS). SNPs were selected as instrumental variables (IVs) by accounting for linkage disequilibrium and removing unbalanced connections. The primary analysis used the inverse variance-weighted (IVW) method with supplementary analyses. Heterogeneity and pleiotropy were assessed using Cochran's Q test, MR-Egger intercept, and MR-PRESSO. Finally, reverse causality was explored. Results The IVW method indicated a causal link between GERD and increased risk of migraine (OR = 1.381, 95% CI: 1.190–1.602, p = 2.04E-05), particularly the MO subtype (OR = 1.600, 95% CI: 1.311–1.953, p = 3.67E-06). No significant association was found for MA (OR = 1.193, 95% CI: 0.983–1.449, p = 0.074). Reverse MR analysis showed no causal relationship between migraine and GERD. Conclusion GERD is causally linked to an increased risk of migraine, especially the MO subtype. No reverse causal relationship was found, highlighting the importance of considering migraine subtypes in understanding their association with GERD.