The association between interatrial shunt and subtypes of migraine: a Mendelian randomization study

Approximately one-quarter of adults have a patent foramen ovale (PFO). Migraine is the second most prevalent neurological disorder. The potential causal relationship between PFO and migraine has been a subject of ongoing debate. This study aims to investigate the genetic association between PFO and migraine. This study utilized aggregated data from the Finnish database to explore the genetic causal relationship between PFO as an exposure factor and migraine as an outcome factor. We employed a MR design, with inverse variance weighting (IVW) as the primary analysis method, supplemented by MR-Egger regression. Sensitivity analyses included Cochran Q tests, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. After screening, we selected four single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for the Mendelian randomization analysis. The IVW analysis revealed statistically significant associations between PFO and five subtypes of migraine: overall migraine (OR = 1.0531, P = 0.0253), migraine with aura (OR = 1.0809, P = 0.0227), triptan use in patients with migraine with aura (OR = 1.0986, P = 0.0355), migraine without aura (OR = 1.0906, P = 0.0209), and triptan use in patients with migraine without aura (OR = 1.1043, P = 0.0220). No evidence of horizontal pleiotropy was detected in the MR-Egger intercept analysis. These findings enhance our understanding of the relationship between PFO and migraine. This study provides preliminary evidence of a positive causal association between PFO and migraine. The analysis suggests that PFO may be associated with an increased risk of migraine.