A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine.



Guo, Yanjun, Rist, Pamela M, Daghlas, Iyas, Giulianini, Franco, International Headache Genetics Consortium, , 23andMe Research Team, , Kurth, Tobias and Chasman, Daniel I
(2020) A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine. Nature communications, 11 (1).

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Abstract

Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10-06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = -0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10-08), nine of which replicate (P < 0.05) in the UK Biobank. Five shared loci (ITGB5, SMG6, ADRA2B, ANKDD1B, and KIAA0040) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15-1.25]/10 mmHg; P = 5.57 × 10-25) on migraine than SBP (1.05 [1.03-1.07]/10 mmHg; P = 2.60 × 10-07) and a corresponding opposite effect for PP (0.92 [0.88-0.95]/10 mmHg; P = 3.65 × 10-07). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.

Item Type: Article
Uncontrolled Keywords: International Headache Genetics Consortium, 23andMe Research Team
Depositing User: Symplectic Admin
Date Deposited: 28 Aug 2020 15:39
Last Modified: 23 Jan 2021 02:11
DOI: 10.1038/s41467-020-17002-0
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3099136