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

Anttila, V., Stefansson, H., Kallela, M., Todt, U., Terwindt, G. M., Calafato, M. S., Nyholt, Dale R., Dimas, A. S., Freilinger, T., Muller-Myhsok, B., Artto, V., Inouye, M., Alakurtti, K., Kaunisto, M. A., Hamalainen, E., de Vries, B., Stam, A. H., Weller, C. M., Heinze, A., Heinze-Kuhn, K., Goebel, I., Borck, G., Gobel, H., Steinberg, S., Wolf, C., Bjornsson, A., Gudmundsson, G., Kirchmann, M., Hauge, A., Werge, T., Schoenen, J., Eriksson, J. G., Hagen, K., Stovner, L., Wichmann, H. E., Meitinger, T., Alexander, M., Moebus, S., Schreiber, S., Aulchenko, Y. S., Breteler, M. M., Uitterlinden, A. G., Hofman, A., van Duijn, C. M., Tikka-Kleemola, P., Vepsalainen, S., Lucae, S., Tozzi, F., Muglia, P., Barrett, J., Kaprio, J., Farkkila, M., Peltonen, L., Stefansson, K., Zwart, J. A., Ferrari, M. D., Olesen, J., Daly, M., Wessman, M., van den Maagdenberg, A. M., Dichgans, M., Kubisch, C., Dermitzakis, E. T., Frants, R. R., & Palotie, A. (2010) Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nature Genetics, 42(10), pp. 869-873.

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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(-)(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 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(-)(5), permuted threshold for genome-wide significance 7.7 x 10(-)(5). To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.

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ID Code: 91997
Item Type: Journal Article
Refereed: Yes
Keywords: Antigens, Surface/genetics, Calcium-Binding Proteins/genetics, Case-Control Studies, Cell Adhesion Molecules/genetics, Cells, Cultured, Chromosomes, Human, Pair 8/*genetics, Female, *Genetic Predisposition to Disease, *Genome, Human, *Genome-Wide Association Study, Genotype, Glutamate Carboxypeptidase II/genetics, Humans, Lymphocytes/metabolism, Male, Microsatellite Repeats/*genetics, Migraine Disorders/*genetics, Quantitative Trait Loci
DOI: 10.1038/ng.652
ISSN: 1546-1718
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 19 Jan 2016 02:35
Last Modified: 12 Feb 2016 03:10

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