[en] 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 x 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 x 10(1)(1) (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 x 10, permuted threshold for genome-wide significance 7.7 x 10. To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.
Disciplines :
Neurology Neurosciences & behavior
Author, co-author :
Anttila, Verneri
Stefansson, Hreinn
Kallela, Mikko
Todt, Unda
Terwindt, Gisela M
Calafato, M Stella
Nyholt, Dale R
Dimas, Antigone S
Freilinger, Tobias
Muller-Myhsok, Bertram
Artto, Ville
Inouye, Michael
Alakurtti, Kirsi
Kaunisto, Mari A
Hamalainen, Eija
de Vries, Boukje
Stam, Anine H
Weller, Claudia M
Heinze, Axel
Heinze-Kuhn, Katja
Goebel, Ingrid
Borck, Guntram
Gobel, Hartmut
Steinberg, Stacy
Wolf, Christiane
Bjornsson, Asgeir
Gudmundsson, Gretar
Kirchmann, Malene
Hauge, Anne
Werge, Thomas
Schoenen, Jean ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Neuro-anatomie
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