Investigating the causal and genetic relationship between migraine and Parkinson's disease

Objective: The relationship between migraine and Parkinson's disease (PD) remains controversial. We aimed to investigate the causal and genetic associations between migraine and PD. Methods: Genetic data for migraine [any migraine (AM), migraine without aura (MO), and migraine with aura (MA)] and PD were sourced from the latest genome-wide meta-analyses conducted by the International Headache Genetics Consortium and the International Parkinson's Disease Genomics Consortium, respectively. Various analyses were performed to evaluate the potential causal associations and explore genetic correlations between these conditions. Results: The analyses indicated that AM (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.91-1.14; p = 0.785), MO (OR 0.94, 95% CI 0.84-1.07; p = 0.358), and MA (OR 1.01, 95% CI 0.95-1.06; p = 0.846) were not significantly associated with the risk of PD. Similarly, reverse analyses also demonstrated no significant causality between PD and the risks of migraine or its subtypes. After adjusting for coronary heart disease, AM (OR 0.99, 95% CI 0.90-1.10; p = 0.897), MO (OR 0.94, 95% CI 0.86-1.03; p = 0.207), and MA (OR 1.00, 95% CI 0.93-1.07; p = 0.902) remained unrelated to PD risk. Likewise, PD was found to be unassociated with AM (OR 0.96, 95% CI 0.92-1.02; p = 0.168), MO (OR 0.95, 95% CI 0.86-1.05; p = 0.287), and MA (OR 1.02, 95% CI 0.93-1.13; p = 0.669). These null findings persisted even when adjusting for hypertension. Apart from above causal inference results, no significant genetic correlation was found between AM (r(g) = -0.06, p = 0.127), MA (r(g) = -0.05, p = 0.516), or MO (r(g) = -0.06, p = 0.492) and PD, and no correlations were observed across specific genomic regions. Additionally, no shared heritability was observed between PD and migraine, or its subtypes, in tissue expression. Conclusion: Our study suggests that there is no significant causal association or genetic correlation between migraine and PD from a genetic perspective.