Migraine is not a risk factor for glaucoma: Evidence from a bidirectional Mendelian randomization study

Numerous compelling observational studies have indicated that migraine is a risk factor for the development of glaucoma. Nevertheless, some studies have observed entirely opposite results. The objective of our research is to evaluate the potential relationship between migraine and glaucoma by employing a bidirectional Mendelian Randomization (MR) approach. This method enables us to rigorously assess the causal links between these 2 conditions, thereby addressing the discrepancies in existing literature. Independent genetic variants associated with glaucoma and migraine at the genome-wide significance level were selected as instrumental variables. All summary data were obtained from the genome-wide association study database. The primary method employed in the bidirectional MR analysis was the inverse variance weighted method, while sensitivity analyses utilized the leave-one-out method, MR-Egger method, and MR-Pleiotropy RESidual Sum and Outlier‌ method. When migraine and its subtypes (specifically migraine with aura and migraine without aura) were evaluated as exposure factors, we found no evidence of a causal relationship with glaucoma and its subtypes (namely angle-closure glaucoma and open-angle glaucoma). Subsequently, in the reverse MR analysis, when glaucoma and its subtypes (angle-closure glaucoma and open-angle glaucoma) were assessed as exposure factors, there was no substantial evidence to support a causal relationship with migraine or its subtypes (migraine with aura and migraine without aura). Furthermore, sensitivity analyses also reinforced the robustness of our bidirectional MR findings. Our bidirectional MR analysis mitigates the biases associated with traditional observational studies, highlighting that there is no direct causal relationship between migraine and the risk of glaucoma.