Appendix: Association between hemostatic profile and migraine: a Mendelian randomization analysis

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, odds ratio[95% confidence interval]=1.05[1.03, 1.08]/standard deviation (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 suscep...