1. A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine
- Author
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Guo, Y. (Yanjun), Rist, P.M. (Pamela M.), Daghlas, I. (Iyas), Giulianini, F. (Franco), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tonu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.D. (Scott D.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Hrafnsdottir, M.G. (Maria Gudlaug), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda W. J. H.), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T. (Thomas), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn M. J. M. van den), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark J.), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel I.), Nyholt, D.R. (Dale R.), Palotie, A. (Aarno), Agee, M. (Michelle), Auton, A. (Adam), Bell, R.K. (Robert K.), Bryc, K. (Katarzyna), Elson, S.L. (Sarah L.), Fontanillas, P. (Pierre), Huber, K.E. (Karen E.), Kleinman, A. (Aaron), Litterman, N.K. (Nadia K.), McCreight, J.C. (Jennifer C.), McIntyre, M.H. (Matthew H.), Mountain, J.L. (Joanna L.), Noblin, E.S. (Elizabeth S.), Northover, C.A.M. (Carrie A. M.), Pitts, S.J. (Steven J.), Sathirapongsasuti, J.F. (J. Fah), Sazonova, O.V. (Olga V.), Shelton, J.F. (Janie F.), Shringarpure, S. (Suyash), Tian, C. (Chao), Tung, J.Y. (Joyce Y.), Vacic, V. (Vladimir), Kurth, K.H. (Karl), Chasman, D.I. (Daniel), Guo, Y. (Yanjun), Rist, P.M. (Pamela M.), Daghlas, I. (Iyas), Giulianini, F. (Franco), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tonu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.D. (Scott D.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Hrafnsdottir, M.G. (Maria Gudlaug), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda W. J. H.), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T. (Thomas), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn M. J. M. van den), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark J.), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel I.), Nyholt, D.R. (Dale R.), Palotie, A. (Aarno), Agee, M. (Michelle), Auton, A. (Adam), Bell, R.K. (Robert K.), Bryc, K. (Katarzyna), Elson, S.L. (Sarah L.), Fontanillas, P. (Pierre), Huber, K.E. (Karen E.), Kleinman, A. (Aaron), Litterman, N.K. (Nadia K.), McCreight, J.C. (Jennifer C.), McIntyre, M.H. (Matthew H.), Mountain, J.L. (Joanna L.), Noblin, E.S. (Elizabeth S.), Northover, C.A.M. (Carrie A. M.), Pitts, S.J. (Steven J.), Sathirapongsasuti, J.F. (J. Fah), Sazonova, O.V. (Olga V.), Shelton, J.F. (Janie F.), Shringarpure, S. (Suyash), Tian, C. (Chao), Tung, J.Y. (Joyce Y.), Vacic, V. (Vladimir), Kurth, K.H. (Karl), and Chasman, D.I. (Daniel)
- 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 (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.
- Published
- 2020
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