Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1.

Authors:
Verneri Anttila, Hreinn Stefansson, Mikko Kallela, Unda Todt, Gisela M Terwindt, M Stella Calafato, Dale R Nyholt, Antigone S Dimas, Tobias Freilinger, Bertram Müller-Myhsok, Ville Artto, Michael Inouye, Kirsi Alakurtti, Mari A Kaunisto, Eija Hämäläinen, Boukje de Vries, Anine H Stam, Claudia M Weller, Axel Heinze, Katja Heinze-Kuhn, Ingrid Goebel, Guntram Borck, Hartmut Göbel, Stacy Steinberg, Christiane Wolf, Asgeir Björnsson, Gretar Gudmundsson, Malene Kirchmann, Anne Hauge, Thomas Werge, Jean Schoenen, Johan G Eriksson, Knut Hagen, Lars Stovner, H-Erich Wichmann, Thomas Meitinger, Michael Alexander, Susanne Moebus, Stefan Schreiber, Yurii S Aulchenko, Monique M B Breteler, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Päivi Tikka-Kleemola, Salli Vepsäläinen, Susanne Lucae, Federica Tozzi, Pierandrea Muglia, Jeffrey Barrett, Jaakko Kaprio, Markus Färkkilä, Leena Peltonen, Kari Stefansson, John-Anker Zwart, Michel D Ferrari, Jes Olesen, Mark Daly, Maija Wessman, Arn M J M van den Maagdenberg, Martin Dichgans, Christian Kubisch, Emmanouil T Dermitzakis, Rune R Frants, Aarno Palotie, - -
Year of publication:
2010
Volume:
42
Issue:
10
Issn:
1061-4036
Journal title abbreviated:
NAT GENET
Journal title long:
Nature genetics
Impact factor:
31.616
Abstract:
Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 × 10⁻⁹, odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 × 10⁻¹¹ (odds ratio = 1.18, 95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 × 10⁻⁵, permuted threshold for genome-wide significance 7.7 × 10⁻⁵. To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.