Association Between Hemostatic Profile and Migraine: A Mendelian Randomization Analysis

Area of Science:

• Genetics
• Cardiovascular Biology
• Neurology

Background:

• Migraine is a common neurological disorder with complex etiology.
• Hemostasis, the process of stopping bleeding, involves a complex system of factors.
• Previous research has suggested potential links between hemostatic factors and migraine, but causal relationships remain unclear.

Purpose of the Study:

• To investigate the potential causal relationship between specific hemostatic measures and the susceptibility to migraine and its subtypes.
• To utilize genetic instrumental analysis to assess causality, minimizing confounding factors.

Main Methods:

• Employed two-sample Mendelian randomization analyses using genome-wide association study (GWAS) summary statistics.
• Examined twelve blood-based hemostasis measures, including levels and activities of eight hemostatic factors and two fibrinopeptides.
• Assessed associations with overall migraine, migraine with aura (MA), and migraine without aura (MO).

Main Results:

• Elevated coagulation factor VIII activity (FVIII), von Willebrand factor (vWF), and phosphorylated fibrinopeptide A were significantly associated with increased migraine susceptibility.
• Fibrinogen levels showed an inverse association with MA, but not overall migraine.
• Sensitivity analyses indicated that effects for fibrinogen and phosphorylated fibrinopeptide A were robust, while FVIII and vWF associations required further investigation due to potential pleiotropy.

Conclusions:

• Findings suggest a potential causal role for increased FVIII, vWF, and phosphorylated fibrinopeptide A in migraine susceptibility.
• Decreased fibrinogen may also contribute to migraine susceptibility, particularly MA.
• These results highlight potential etiological links between hemostatic system function and migraine pathogenesis.