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

Research output: Contribution to journalJournal articlepeer-review

  • Yanjun Guo
  • Pamela M. Rist
  • Iyas Daghlas
  • Franco Giulianini
  • Padhraig Gormley
  • Verneri Anttila
  • Bendik S. Winsvold
  • Priit Palta
  • Tonu Esko
  • Pers, Tune H
  • Kai How Farh
  • Ester Cuenca-Leon
  • Mikko Muona
  • Nicholas A. Furlotte
  • Tobias Kurth
  • Andres Ingason
  • George McMahon
  • Lannie Ligthart
  • Gisela M. Terwindt
  • Mikko Kallela
  • Tobias M. Freilinger
  • Caroline Ran
  • Scott G. Gordon
  • Anine H. Stam
  • Stacy Steinberg
  • Guntram Borck
  • Markku Koiranen
  • Lydia Quaye
  • Hieab H.H. Adams
  • Terho Lehtimäki
  • Antti Pekka Sarin
  • Juho Wedenoja
  • David A. Hinds
  • Julie E. Buring
  • Markus Schürks
  • Paul M. Ridker
  • Maria Gudlaug Hrafnsdottir
  • Hreinn Stefansson
  • Susan M. Ring
  • Jouke Jan Hottenga
  • Brenda W.J.H. Penninx
  • Markus Färkkilä
  • Ville Artto
  • Mari Kaunisto
  • Salli Vepsäläinen
  • Rainer Malik
  • Anne Francke Christensen
  • Hansen, Thomas Folkmann
  • Werge, Thomas
  • Olesen, Jes
  • The International Headache Genetics Consortium
  • the 23andMe Research Team

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.

Original languageEnglish
Article number3368
JournalNature Communications
Volume11
Issue number1
ISSN2041-1723
DOIs
Publication statusPublished - 2020

ID: 251692593