Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine
Authors: 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 HH , 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 WJH , Färkkilä Markus , Artto Ville , Kaunisto Mari , Vepsäläinen Salli , Malik Rainer , Heath Andrew C , Madden Pamela A F , Martin Nicholas G , Montgomery Grant W , 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 , van Duijn Cornelia M , 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 , van den Maagdenberg Arn MJM , 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 ,   on behalf of the International Headache Genetics Consortium
Published: November 2015

AbstractMigraine is a debilitating neurological disorder affecting around 1 in 7 people worldwide, but its molecular mechanisms remain poorly understood. Some debate exists over 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 performed the largest genetic study of migraine to date, comprising 59,674 cases and 316,078 controls from 22 GWA studies. We identified 45 independent single nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P< 5 × 10−8) that map to 38 distinct genomic loci, including 28 loci not previously reported and the first locus identified on chromosome X. Furthermore, a subset analysis for migraine without aura (MO) identified seven of the same loci as from the full sample, whereas no loci reached genome-wide significance in the migraine with aura (MA) subset. In subsequent computational analyzes, 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.