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

Publikation: Bidrag til tidsskriftLetterForskningfagfællebedømt

  • 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
  • Werge, Thomas
  • 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
  • Olesen, Jes
  • International Headache Genetics Consortium
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¿¿, 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.
OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind42
Udgave nummer10
Sider (fra-til)869-73
Antal sider5
ISSN1061-4036
DOI
StatusUdgivet - 1 okt. 2010

ID: 34083626