Abstract
Objective: To assess support for a causal relationship between hemostatic measures and migraine susceptibility using genetic instrumental analysis.
Methods: Two-sample Mendelian randomization (MR) instrumental leveraging available genome-wide association study (GWAS) summary statistics was applied to hemostatic measures as potential causal for migraine and its subtypes, migraine with aura (MA) and migraine without aura (MO). Twelve blood-based measures of hemostasis were examined, including plasma level or activity of eight hemostatic factors and two fibrinopeptides together with two hemostasis clinical tests.
Results: There were significant instrumental effects between increased coagulation factor VIII activity (FVIII, OR [95% CI]=1.05[1.03, 1.08]/SD, P=6.08×10-05), von Willebrand factor level (VWF, 1.05[1.03, 1.08]/SD, P=2.25×10-06), and phosphorylated fibrinopeptide A level (1.13[1.07, 1.19]/SD, P=5.44×10-06) with migraine susceptibility. When extended to migraine subtypes, FVIII, VWF, and phosphorylated fibrinopeptide A showed slightly stronger effects with MA than overall migraine. Fibrinogen level was inversely linked with MA (0.76[0.64, 0.91]/SD, P=2.32×10-03) but not overall migraine. None of the hemostatic factors was linked with MO. In sensitivity analysis, effects for fibrinogen and phosphorylated fibrinopeptide A were robust, while independent effects of FVIII and VWF could not be distinguished, and FVIIII associations were potentially affected by pleiotropy at the ABO locus. Causal effects from migraine to the hemostatic measures were not supported in reverse MR. However, MA was not included due to lack of instruments.
Conclusions: The findings support potential causality of increased FVIII, VWF, and phosphorylated fibrinopeptide A, and decreased fibrinogen in migraine susceptibility, especially for MA, potentially revealing etiologic relationships between hemostasis and migraine.
- Received August 27, 2020.
- Accepted in final form February 24, 2021.
- © 2021 American Academy of Neurology
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