A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine
Yanjun Guo, Pamela M. Rist, Iyas Daghlas, Franco Giulianini, Padhraig Gormley, Verneri Anttila, Bendik S. Winsvold, Priit Palta, Tõnu Esko, Tune H. Pers, Kai-How Farh, Ester Cuenca-León, Mikko Muona, Nicholas A. Furlotte, Tobias Kurth, Andrés Ingason, George McMahon, Lannie Ligthart, Gisela M. Terwindt, Mikko Kallela, Tobias 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 Stefánsson, Susan M. Ring, Jouke‐Jan Hottenga, Brenda W.J.H. Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C. Heath, Pamela A. F. Madden, Nicholas G. Martin, Grant W. Montgomery, Mitja Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H. Lee, Cynthia Sandor, Caleb Webber, M. Zameel Cader, Bertram Müller‐Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G. Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, André G. Uitterlinden, Albert Hofman, Cornelia M. van Duijn, Lynn Cherkas, Linda M. Pedersen, Audun Stubhaug, Christopher Sivert Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo Aromaa, Olli T. Raitakari, M. Arfan Ikram, Tim D. Spector, Marjo‐Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P. Strachan, Michel D. Ferrari, Andrea Carmine Belin, Martin Dichgans, Maija Wessman, Arn M. J. M. van den Maagdenberg
Abstract
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 cases / N controls = 59,674/316,078) and BP ( N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, r g = 0.11, P = 3.56 × 10 −06 ) and systolic BP (SBP, r g = 0.06, P = 0.01), but not pulse pressure (PP, r g = −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.