Abstracts

Rationale: Epilepsy and migraine are both episodic disorders and highly heritable diseases. They share similar clinical features as well as pathophysiological mechanisms. We conducted a bidirectional Mendelian randomization (MR) analysis expecting to providing clues to clinical diagnosis and treatment in the future.

Methods: Genome-wide association studies (GWAS) summary statistics for epilepsy were collected from ILAE Consortium (29,944 cases and 52,538 controls). GWAS summary statistics for migraine were downloaded from e International Headache Genetics Consortium (59,674 cases vs 316,078 controls). Two epilepsy phenotypes (focal and generalized epilepsy) and two migraine phenotypes (migraine with and without aura) were considered. MR analyses were conducted by the inverse variance weighted (IVW) method.


Results: A combination of MR analyses suggested a possible causal association from genetic liability for epilepsy to migraine risk (OR 6.885, 95% CI [5.089-9.316], < 0.001). However, due to the detection of pleiotropy by MR-Egger and considerations related to the threshold for genetic instruments, a cautious approach is warranted in interpreting the result. The generalized epilepsy was also associated with higher risk of migraine without migraine (OR 5.576, 95% CI [1.176-26.431], =0.030), and heterogeneity assessments confirmed the results' robustness. For other relationships, there was no reliable supporting data available.


Conclusions: This study provided new evidence to explain the observed epilepsy-migraine comorbidity. It emphasized that the monitoring of migraine risk in patients with epilepsy should be strengthened in clinical practice, especially migraine without aura in patients with generalized epilepsy.

Funding: This research was supported by the National Natural Science Foundation of China (82271500).