Association Between Hemostatic Profile and Migraine
Year: 2021
Type: article
Study design: Observational Study
Abstract: Objective To assess support for a causal relationship between hemostatic measures and migraine susceptibility using genetic instrumental analysis. Methods Two-sample Mendelian randomization instrumental analyses leveraging available genome-wide association study (GWAS) summary statistics were applied to hemostatic measures as potentially 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 8 hemostatic factors and 2 fibrinopeptides together with 2 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]/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, whereas independent effects of FVIII and vWF could not be distinguished, and FVIII associations were potentially affected by pleiotropy at the ABO locus. Causal effects from migraine to the hemostatic measures were not supported in reverse Mendelian randomization. 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.
Source: Neurology
Institutions: Brigham and Women's Hospital, Harvard University, Kaiser Permanente Washington Health Research Institute, University of Washington, Hospital de Sant Pau, VA Office of Research and Development, Karolinska Institutet, Seattle Epidemiologic Information and Research Center, The University of Texas Health Science Center at Houston
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Population genomic variation, functional biology, and the risk of venous thrombosis, Effects of Vitamin D and Omega-3 on Cerebrovascular Disease, Causality and/or shared physiology linking plasma lipids and blood pressure to migraine, Using genomics and functional biology to understand fibrinogen and factor XIII and their effects on thrombotic diseases, Analysis of Whole Genome Sequence and Hemostasis Phenotypes
OpenAlex ID: W3152003038