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Guo, Yanjun; Rist, Pamela M.; Daghlas, Iyas; Giulianini, Franco; Gormley, Padhraig; Anttila, Verneri; Winsvold, Bendik S.; Palta, Priit; Esko, Tonu; Pers, Tune H.; Farh, Kai-How; Cuenca-Leon, Ester; Muona, Mikko; Furlotte, Nicholas A.; Kurth, Tobias; Ingason, Andres; McMahon, George; Ligthart, Lannie; Terwindt, Gisela M.; Kallela, Mikko; Freilinger, Tobias M.; Ran, Caroline; Gordon, Scott G.; Stam, Anine H.; [...]

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

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  • Media type: E-Article
  • Title: A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine
  • Contributor: Guo, Yanjun; Rist, Pamela M.; Daghlas, Iyas; Giulianini, Franco; Gormley, Padhraig; Anttila, Verneri; Winsvold, Bendik S.; Palta, Priit; Esko, Tonu; Pers, Tune H.; Farh, Kai-How; Cuenca-Leon, Ester; Muona, Mikko; Furlotte, Nicholas A.; Kurth, Tobias; Ingason, Andres; McMahon, George; Ligthart, Lannie; Terwindt, Gisela M.; Kallela, Mikko; Freilinger, Tobias M.; Ran, Caroline; Gordon, Scott G.; Stam, Anine H.; [...]
  • imprint: Springer Science and Business Media LLC, 2020
  • Published in: Nature Communications, 11 (2020) 1
  • Language: English
  • DOI: 10.1038/s41467-020-17002-0
  • ISSN: 2041-1723
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>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 (<jats:italic>N</jats:italic><jats:sub>cases</jats:sub>/<jats:italic>N</jats:italic><jats:sub>controls</jats:sub> = 59,674/316,078) and BP (<jats:italic>N</jats:italic> = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, <jats:italic>r</jats:italic><jats:sub>g</jats:sub> = 0.11, <jats:italic>P</jats:italic> = 3.56 × 10<jats:sup>−06</jats:sup>) and systolic BP (SBP, <jats:italic>r</jats:italic><jats:sub>g</jats:sub> = 0.06, <jats:italic>P</jats:italic> = 0.01), but not pulse pressure (PP, <jats:italic>r</jats:italic><jats:sub>g</jats:sub> = −0.01, <jats:italic>P</jats:italic> = 0.75). Cross-trait meta-analysis reveals 14 shared loci (<jats:italic>P</jats:italic> ≤ 5 × 10<jats:sup>−08</jats:sup>), nine of which replicate (<jats:italic>P</jats:italic> &lt; 0.05) in the UK Biobank. Five shared loci (<jats:italic>ITGB5</jats:italic>, <jats:italic>SMG6</jats:italic>, <jats:italic>ADRA2B</jats:italic>, <jats:italic>ANKDD1B</jats:italic>, and <jats:italic>KIAA0040</jats:italic>) 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; <jats:italic>P</jats:italic> = 5.57 × 10<jats:sup>−25</jats:sup>) on migraine than SBP (1.05 [1.03–1.07]/10 mmHg; <jats:italic>P</jats:italic> = 2.60 × 10<jats:sup>−07</jats:sup>) and a corresponding opposite effect for PP (0.92 [0.88–0.95]/10 mmHg; <jats:italic>P</jats:italic> = 3.65 × 10<jats:sup>−07</jats:sup>). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.</jats:p>
  • Access State: Open Access