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

Tobias Freilinger, Verneri Anttila, Boukje De Vries, Rainer Malik, Mikko Kallela, Gisela M. Terwindt, Patricia Pozo-Rosich, Bendik Winsvold, Dale R. Nyholt, Willebrordus P.J. Van Oosterhout, Ville Artto, Unda Todt, Eija Hämäläinen, Jèssica Fernández-Morales, Mark A. Louter, Mari A. Kaunisto, Jean Schoenen, Olli Raitakari, Terho Lehtimäki, Marta Vila-PueyoHartmut Göbel, Erich Wichmann, Cèlia Sintas, Andre G. Uitterlinden, Albert Hofman, Fernando Rivadeneira, Axel Heinze, Erling Tronvik, Cornelia M. Van Duijn, Jaakko Kaprio, Bru Cormand, Maija Wessman, Rune R. Frants, Thomas Meitinger, Bertram Müller-Myhsok, John Anker Zwart, Markus Färkkilä, Alfons MacAya, Michel D. Ferrari, Christian Kubisch, Aarno Palotie, Martin Dichgans, Arn M.J.M. Van Den Maagdenberg

    Research output: Contribution to journalArticleResearchpeer-review

    250 Citations (Scopus)


    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 × 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 × 10-4; combined P = 7.06 × 10-11) and at 3p24 (near TGFBR2; replication P = 1.0 × 10-4; combined P = 1.17 × 10-9). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 × 10-8 and P = 0.02; combined P = 3.86 × 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. © 2012 Nature America, Inc. All rights reserved.
    Original languageEnglish
    Pages (from-to)777-782
    JournalNature Genetics
    Issue number7
    Publication statusPublished - 1 Jul 2012


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