Genome-wide association analysis identifies susceptibility loci for migraine without aura

Freilinger, T., Anttila, V., de Vries, B., Malik, R., Kallela, M., Terwindt, G.M., Pozo-Rosich, P., Winsvold, B., Nyholt, D.R., van Oosterhout, W.P., Artto, V., Todt, U., Hamalainen, E., Fernandez-Morales, J., Louter, M.A., Kaunisto, M.A., Schoenen, J., Raitakari, O., Lehtimaki, T., Vila-Pueyo, M., Gobel, H., Wichmann, E., Sintas, C., Uitterlinden, A.G., Hofman, A., Rivadeneira, F., Heinze, A., Tronvik, E., van Duijn, C.M., Kaprio, J., Cormand, B., Wessman, M., Frants, R.R., Meitinger, T., Muller-Myhsok, B., Zwart, J.A., Farkkila, M., Macaya, A., Ferrari, M.D., Kubisch, C., Palotie, A., Dichgans, M., & van den Maagdenberg, A.M. (2012) Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nature Genetics, 44(7), pp. 777-782.

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Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 x 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 x 10(-4); combined P = 7.06 x 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 x 10(-4); combined P = 1.17 x 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 x 10(-8) and P = 0.02; combined P = 3.86 x 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder.

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ID Code: 91845
Item Type: Journal Article
Refereed: No
Keywords: Adult, Case-Control Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study/methods, Humans, Low Density Lipoprotein Receptor-Related Protein-1/genetics, MADS Domain Proteins/genetics, MEF2 Transcription Factors, Male, Microfilament Proteins/genetics, Migraine without Aura/*genetics, Myogenic Regulatory Factors/genetics, Polymorphism, Single Nucleotide, Protein-Serine-Threonine Kinases/genetics, Receptors, Transforming Growth Factor beta/genetics, TRPM Cation Channels/genetics
DOI: 10.1038/ng.2307
ISSN: 1546-1718
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 13 Jan 2016 04:38
Last Modified: 14 Jan 2016 01:57

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