Effect of genetic liability to migraines on spontaneous coronary artery dissection and fibromuscular dysplasia.

Background: Associations among migraines, spontaneous coronary artery dissection (SCAD), and fibromuscular dysplasia (FMD) have been reported; however, their causality is inconclusive.

Methods: We inferred a causal relation between exposure (migraines) and outcomes (SCAD and FMD) using two-sample MR analysis. Mediation analysis was performed using reverse and multivariate MR analysis methods. Finally, using two-sample MR analysis, we explored whether the currently perceived potential risk factors for SCAD and FMD mediate the aforementioned causal association.

Results: Inverse Variance Weighted (IVW) analysis showed that migraines increased the risk of developing SCAD and FMD. SCAD increases the risk of developing FMD. Reverse causality or pleiotropy was not observed. Multivariate random IVW analysis showed that the effect of migraine on FMD was no longer significant in the multivariate model, whereas the effect of SCAD remained significant. SCAD mediated the causal association between migraine and FMD, with a mediating effect of 0.119 and a proportion of 18.30 %. IVW analyses did not find direct evidence that these associations were consistently related to other potential pathogenic factors of SCAD or FMD.

Conclusions: Migraines are a risk factor for both SCAD and FMD, whereas SCAD is an incomplete mediator of the causal relation between migraine and FMD. However, mechanistic studies are warranted to investigate this link.