A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine
Authors: Guo Yanjun , Rist Pamela M. , Daghlas Iyas , Giulianini Franco ,   The International Headache Genetics Consortium, 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. , Steinberg Stacy , Borck Guntram , Koiranen Markku , Quaye Lydia , Adams Hieab H. H. , Lehtimäki Terho , Sarin Antti-Pekka , Wedenoja Juho , Hinds David A. , Buring Julie E. , Schürks Markus , Ridker Paul M. , Hrafnsdottir Maria Gudlaug , Stefansson Hreinn , Ring Susan M. , Hottenga Jouke-Jan , Penninx Brenda W. J. H. , Färkkilä Markus , Artto Ville , Kaunisto Mari , Vepsäläinen Salli , Malik Rainer , Heath Andrew C. , Madden Pamela A. F. , Martin Nicholas G. , Montgomery Grant W. , Kurki Mitja , Kals Mart , Mägi Reedik , Pärn Kalle , Hämäläinen Eija , Huang Hailiang , Byrnes Andrea E. , Franke Lude , Huang Jie , Stergiakouli Evie , Lee Phil H. , Sandor Cynthia , Webber Caleb , Cader Zameel , Muller-Myhsok Bertram , Schreiber Stefan , Meitinger Thomas , Eriksson Johan G. , Salomaa Veikko , Heikkilä Kauko , Loehrer Elizabeth , Uitterlinden Andre G. , Hofman Albert , Duijn Cornelia M. van , Cherkas Lynn , Pedersen Linda M. , Stubhaug Audun , Nielsen Christopher S. , Männikkö Minna , Mihailov Evelin , Milani Lili , Göbel Hartmut , Esserlind Ann-Louise , Christensen Anne Francke , Hansen Thomas Folkmann , Werge Thomas , Kaprio Jaakko , Aromaa Arpo J. , Raitakari Olli , Ikram M. Arfan , Spector Tim , Järvelin Marjo-Riitta , Metspalu Andres , Kubisch Christian , Strachan David P. , Ferrari Michel D. , Belin Andrea C. , Dichgans Martin , Wessman Maija , Maagdenberg Arn M. J. M. van den , Zwart John-Anker , Boomsma Dorret I. , Smith George Davey , Stefansson Kari , Eriksson Nicholas , Daly Mark J. , Neale Benjamin M. , Olesen Jes , Chasman Daniel I. , Nyholt Dale R. , Palotie Aarno ,   The 23andMe Research Team, Agee Michelle , Auton Adam , Bell Robert K. , Bryc Katarzyna , Elson Sarah L. , Fontanillas Pierre , Furlotte Nicholas A. , Hinds David A. , Huber Karen E. , Kleinman Aaron , Litterman Nadia K. , McCreight Jennifer C. , McIntyre Matthew H. , Mountain Joanna L. , Noblin Elizabeth S. , Northover Carrie A. M. , Pitts Steven J. , Sathirapongsasuti J. Fah , Sazonova Olga V. , Shelton Janie F. , Shringarpure Suyash , Tian Chao , Tung Joyce Y. , Vacic Vladimir , Kurth Tobias , Chasman Daniel I. 
Published: July 2020

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.