This article is part of the supplement: Abstract Book of The European Headache and Migraine Trust International Congress

Open Access Poster presentation

Migraine without aura: genome-wide association analysis identifies several novel susceptibility

Boukje de Vries1*, Tobias Freilinger2,3, Verneri Anttila4,5, Rainer Malik1, Mikko Kallela6, Gisela M Terwindt7, Patricia Pozo-Rosich8,9, Bendik Winsvold10,4, Dale R Nyholt11, Willebrordus PJ van Oosterhout7, Ville Artto6, Unda Todt12, Eija Hämäläinen4,5, Jèssica Fernández-Morales4,9, Mark A Louter13,7, Mari A Kaunisto14,5, Jean Schoenen15, Olli Raitakari16, Terho Lehtimäki17, Marta Vila-Pueyo18, Hartmut Göbel19, Erich Wichmann20, Cèlia Sintas21,22, Andre G Uitterlinden23, Albert Hofman24, Fernando Rivadeneira23,24, Axel Heinze19, Erling Tronvik25, Cornelia M van Duijn24, Jaakko Kaprio26,27,5, Bru Cormand21,22,28, Maija Wessman14,5, Rune R Frants1, Thomas Meitinger29,30, Bertram Müller-Myhsok31, John-Anker Zwart10, Markus Färkkilä6, Alfons Macaya18, Michel D Ferrari7, Christian Kubisch12, Aarno Palotie32,33,34,4,5, Martin Dichgans2, Arn MJM van den Maagdenberg1,7 and International Headache Genetics Consortium1

  • * Corresponding author: Boukje de Vries

  • † Equal contributors

Author Affiliations

1 Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands

2 Institute for Stroke and Dementia Research, Klinikum der Universität München, Munich, Germany

3 Department of Neurology, Klinikum der Universität München, Munich, Germany

4 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK

5 Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

6 Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland

7 Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands

8 Department of Neurology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain

9 Headache Research Group, Vall d'Hebron Research Institute, Universitat Autonoma de Barcelona, Barcelona, Spain

10 Department of Neurology, Oslo University Hospital and University of Oslo, Oslo, Norway

11 Neurogenetics Laboratory, Queensland Institute of Medical Research, Brisbane, Australia

12 Institute of Human Genetics, University of Ulm, Ulm, Germany

13 Department of Psychiatry, Leiden University Medical Centre, Leiden, The Netherlands

14 Folkhälsan Research Center, Helsinki, Finland

15 Headache Research Unit, Department of Neurology and Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA)-Neurosciences, Liège University, Liège, Belgium

16 Department of Clinical Physiology, University of Turku and Turku University Central Hospital, Turku, Finland

17 Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Tampere, Finland

18 Pediatric Neurology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain

19 Kiel Pain and Headache Center, Kiel, Germany

20 Institute of Epidemiology, Helmholtz Center Munich, Neuherberg, Germany

21 Department of Genetics, University of Barcelona, Barcelona, Spain

22 Biomedical Network Research Centre on Rare Diseases (CIBERER), Barcelona, Spain

23 Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

24 Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands

25 Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway

26 Department of Public Health, University of Helsinki, Helsinki, Finland

27 Department of Mental Health and Alcohol Research, National Institute for Health and Welfare, Helsinki, Finland

28 Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain

29 Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany

30 Institute of Human Genetics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

31 Max Planck Institute of Psychiatry, Munich, Germany

32 The Broad Institute of MIT and Harvard, Boston, Massachusetts, USA

33 Department of Medical Genetics, University of Helsinki, Helsinki, Finland

34 Department of Medical Genetics, Helsinki University Central Hospital, Helsinki, Finland

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The Journal of Headache and Pain 2013, $article.volume.volumeNumber(Suppl 1):P18 doi:10.1186/1129-2377-1-S1-P18


The electronic version of this article is the complete one and can be found online at: http://www.thejournalofheadacheandpain.com/content/1/S1/P18


Published:21 February 2013

© 2013 de Vries et al; licensee Springer.

Introduction

Genome-wide association studies (GWAS) are a novel and promising method to study genetic susceptibility factors for common disorders, including migraine.

Objective

Here we performed the first GWAS in migraine without aura (MO), which is the most common form of migraine.

Methods

To identify common genetic variants for this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch patients and 4,580 population-matched controls. Loci with two or more SNPs with P-values < 1 x 10-5 were selected for follow-up in 2,508 Dutch, Spanish, Finnish and Norwegian patients and 2,652 controls.

Results

Meta-analysis of the discovery and replication data yielded four genome-wide significant (P < 5 x 10-8) MO susceptibility loci in or nearby MEF2D, PHACTR1, ASTN2 and TGFBR2. In addition, SNPs in two loci (in or near TRPM8 and LRP1) that were previously identified in a GWAS on population-based migraine were significantly replicated in our clinic-based MO cohort.

Conclusion

This study reveals the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder.