Causality between migraine and cardiovascular disease: a bidirectional Mendelian randomization study

Abstract Background While growing evidence suggests a relationship between migraine and cardiovascular disease, the genetic evidence for a causal relationship between migraine and cardiovascular disease is still scarce. Investigating the causal association between migraine and cardiovascular disease is vital. Methods We carried out a bidirectional Mendelian randomization (MR) study including discovery samples and replication samples using publicly available genome-wide association study (GWAS) summary datasets and stringent screening instrumental variables. Four different MR techniques—Inverse variance weighted (IVW), MR ‒Egger, weighted median, and weighted mode—as well as various sensitivity analyses—Cochran’s Q, IVW radial, leave-one-out (LOO), and MR-PRESSO—were utilized to investigate the causal relationship between cardiovascular disease and migraine. Results The protective causal effects of genetically predicted migraine on coronary artery disease (OR, 0.881; 95% CI 0.790–0.982; p = 0.023) and ischemic stroke (OR, 0.912; 95% CI 0.854–0.974; p = 0.006) were detected in forward MR analysis but not in any other cardiovascular disease. Consistently, we also discovered protective causal effects of coronary atherosclerosis (OR, 0.865; 95% CI 0.797–0.940; p = 0.001) and myocardial infarction (OR, 0.798; 95% CI 0.668–0.952; p = 0.012) on migraine in reverse MR analysis. Conclusion We found a potential protective effect of migraine on coronary artery disease and ischemic stroke and a potential protective effect of coronary atherosclerosis and myocardial infarction on migraine. We emphasised epidemiological and genetic differences and the need for long-term safety monitoring of migraine medications and future research to improve cardiovascular outcomes in migraine patients.