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Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

2016; Nature Portfolio; Volume: 48; Issue: 8 Linguagem: Inglês

10.1038/ng.3598

1546-1718

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 D. 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, Martti Färkkilâ, 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 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, John‐Anker Zwart, Dorret I. Boomsma, George Davey Smith, Kāri Stefánsson, Nicholas Eriksson, Mark J. Daly, Benjamin M. Neale, Jes Olesen, Daniel I. Chasman, Dale R. Nyholt, Aarno Palotie,

Biochemical effects in animals

Aarno Palotie and colleagues present results of a large genome-wide association study of migraine. They identified significant associations at 38 distinct loci and found enrichment for genes expressed in vascular and smooth muscle tissues. Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10−8) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.