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; Chasman, Daniel I · Nat Commun · 2020

meta_analysis · Level I

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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 (N<sub>cases</sub>/N<sub>controls</sub> = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, r<sub>g</sub> = 0.11, P = 3.56 × 10<sup>-06</sup>) and systolic BP (SBP, r<sub>g</sub> = 0.06, P = 0.01), but not pulse pressure (PP, r<sub>g</sub> = -0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10<sup>-08</sup>), 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<sup>-25</sup>) on migraine than SBP (1.05 [1.03-1.07]/10 mmHg; P = 2.60 × 10<sup>-07</sup>) and a corresponding opposite effect for PP (0.92 [0.88-0.95]/10 mmHg; P = 3.65 × 10<sup>-07</sup>). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.

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