Kiel, Helsinki, Oslo, Cambridge (MA), June 20, 2016. In the most extensive migraine study so far, 44 new gene variants were discovered. They are associated with an increased risk of migraines. Numerous of these gene variants are localized in the areas of the genetic engineering that regulate the brain's bloodstream system. The new discoveries indicate that a disturbance in the brain's blood supply is essential for the development of migraines. The results are published today in the science journal "Nature Genetics". They are a milestone for understanding the causes of migraines.

The project was carried out over several years by scientists in the international headache genetics consortium with the participation of researchers from the Pain Clinic Kiel in cooperation with Prof. Christian Kubisch, Institute for Human Genetics at the University of Hamburg. Prof. Stefan Schreiber, Institute for Clinical Molecular Biology at the University, is also involved from Kiel. Worldwide research teams from Australia, Denmark, Estonia, Finland, Germany, Iceland, Netherlands, Norway, Spain, Sweden, UK and USA have worked. The study is based on genetic makeup samples from 375,000 Europeans, Americans and Australians.

The causes of migraines have been the subject of intensive scientific research for decades. The new study now discovered genetic variants for the first time, which suggests a special reaction of the brain's blood circulation system as the main cause of the migraine formation.

Prof. Hartmut Göbel (58), director of the pain clinic Kiel and co-author, said: “The data of our study for the first time show that the reaction of the arteries and the smooth muscles in the vascular walls of the bloodstream system is essential for migraine development. The arteries supply the nerve cells of the brain with oxygen and energy. Disruption of the supply due to the special genetic equipment of those affected during the migraine attack, according to the new data, plays a crucial role in the triggering of migraine attacks. ”

According to the World Health Organization, migraines are at sixth place of human diseases. Overall, headache diseases occupy the third place of the most severely disabling diseases worldwide. Around one million people per day suffer from migraine attacks in Germany alone. Of these, 100,000 a day are bedridden. Over a billion people are affected worldwide.

Migraines requires very heavy pulsating, throbbing headaches. Physical activity increases the pain so that patients are bound to the bed. You cannot participate in social and professional life. The attacks can be accompanied by severe nausea and insatiable vomiting. Light, noise, noise and general sensitivity to sensory sensitivity make the seizures more difficult. In over 10% of those affected, the attacks of neurological failures such as severe visual disturbances, paralysis, speech disorders or disorders of consciousness can be initiated. Serious complications of migraines include stroke, epileptic seizures and mental comorbidities. In Germany alone, 8.3 million people per day are taken to treat severe headaches.

In epidemiological studies in recent years, it was confirmed that migraines are associated with an increased risk of stroke, heart attack and other diseases of the cardiovascular system.

The new data for migraine formation match these findings. For the first time, the current study revealed that a variant of the Phactr1 gene is associated with an increased risk of migraines. The same gene variant requires an increased risk of tearing the artery wall in the neck area. This is referred to as a cervical arterial dissection and is an important cause of stroke in young patients.

The 44 gene variants now identified are localized on 38 genes. For the first time, the study has uncovered 28 completely unknown gene variants, which play an important role in migraine development. In addition, other known gene variants have been confirmed.

For the uncovering of these new gene variants, the researchers combined data from over 22 genome -wide association studies. They included data from around 35,000 migraine patients. Of the several million genetic variants that were analyzed, 38 independent genome regions that are associated with an increased risk of migraines could be discovered. Only 10 of these regions were known so far.

Since the individual gene variants only slightly increase the risk of migraines, the new results could only be achieved by bringing their samples and analyzes together worldwide. For this reason, international cooperation is crucial for the detection of the complex neurological peculiarities on which the development of migraines is based.

The new genetic findings and analyzes now enable the first concrete steps for the development of individually personalized treatment of the complex folk disease migraine. Even today, over 30 different migraine sub -forms are clinically differentiated. Migraine patients respond very differently to different therapy methods. Medicines that are very effective for part of those affected can be ineffective in other patients. The newly discovered findings can be the basis for dividing those affected into different genetic risk groups. Selective therapy approaches can then develop the best possible therapy methods for the respective sub -group with special genetic patterns. This can lead to a much more effective and compatible prevention and acute therapy of migraine attacks.

Original publication:
Meta-Analysis of 375,000 individuals identifies 38 susceptibility loci for migraine (2016). Padhraig Gormley, Verneri Anttila, Bendik s Winsvold et al. Nature genetics
http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3598.html

More information:
Prof. Hartmut Göbel
Tel: 0431-20099150
E-Mail: hg@schmerzklinik.de

Press Release University of Helsinki: Large-Scale Genetic Study Provides New Insight into the Causes of Migraine

Radio Podcast Prof. Hartmut Göbel, Pain Clinic Kiel: Genetic foundations of migraines: Importance of the new study for research and treatment

Radio Podcast Prof. Dale Nyholt, Queensland University of Technology: World's largest ever migraine study identifies genetic regions linked to their onset

Participating centers

Padhraig Gormley* ,1,2,3,4 , Verneri Anttila* ,2,3,5 , Bendik S Winsvold 6,7,8 , Priit Palta 9 , Tonu Esko 2,10,11 , Tune H. Pers 2,11 ,12,13 , Kai-How Farh 2,5,14 , Ester Cuenca-Leon 1,2,3,15 , Mikko Muona 9,16,17,18 , Nicholas A Furlotte 19 , Tobias Kurth 20,21 , Andres Ingason 22 , George McMahon 23 , Lannie Ligthart 24 , Gisela M Terwindt 25 , Mikko Kallela 26 Tobias M Freilinger 27,28 , Caroline Ran 29 , Scott G Gordon 30 , Anine H Stam 25 , Stacy Steinberg 22 , Guntram Borck 31 , Markku Koiranen 32 , Lydia Quaye 33 , Hieab HH Adams 34.35 , Terho Lehtimäki 36 , Antti-Pekka Sarin 9 , Juho Wedenoja 37 , David A Hinds 19 , Julie E Buring 21.38 , Markus Schürks 39 , Paul M Ridker 21.38 , Maria Gudlaug Hrafnsdottir 40 , Hreinn Stefansson 22 , Susan M Ring 23 , Jouke-Jan Hottenga 24 Brenda WJH Penninx 41 , Markus Färkkilä 26 , Ville Artto 26 , Mari Kaunisto 9 , Salli Vepsäläinen 26 , Rainer Malik 27 , Andrew C Heath 42 , Pamela AF Madden 42 , Nicholas G Martin 30 , Grant W Montgomery 30 , Mitja Kurki 1,2,3 , Mart Kals 10 , Reedik Mägi 10 , Kalle Pärn 10 , Eija Hämäläinen 9 , Hailiang Huang 2,3,5 , Andrea E Byrnes 2,3,5 , Lude Franke 43 , Jie Huang 4 , Evie Stergiakouli 23 , Phil H Lee 1,2,3 , Cynthia Sandor 44 , Caleb Webber 44 , Zameel Cader 45,46 , Bertram Muller-Myhsok 47 , Stefan Schreiber 48 , Thomas Meitinger 49 , Johan G Eriksson 50.51 , Veikko Salomaa 51 , Kauko Heikkilä 52 , Elizabeth Loehrer 34.53 , Andre G Uitterlinden 54 Albert Hofman 34 , Cornelia M van Duijn 34 , Lynn Cherkas 33 , Linda M. Pedersen 6 , Audun Stubhaug 55.56 , Christopher S Nielsen 55.57 , Minna Männikkö 32 , Evelin Mihailov 10 , Lili Milani 10 , Hartmut Göbel 58 , Ann-Louise Esserlind 59 , Anne Francke Christensen 59 , Thomas Folkmann Hansen 60 , Thomas Werge 61, 62.63 , International Headache Genetics Consortium 64 , Jaakko Kaprio 9,65,66 , Arpo J Aromaa 51 , Olli Raitakari 67.68 , M Arfan Ikram 34,35,68 , Tim Spector 33 , Marjo-Riitta Järvelin 32.70, 71.72 , Andres Metspalu 10 , Christian Kubisch 73 , David P Strachan 74 , Michel D Ferrari 25 , Andrea C Belin 29 , Martin Dichgans 27.75 , Maija Wessman 9.16 , Arn MJM van den Maagdenberg 25.76 , John- Anker Zwart 6,7,8 , Dorret I Boomsma 24 , George Davey Smith 23 , Kari Stefansson 22,77 , Nicholas Eriksson 19 , Mark J Daly 2,3,5 , Benjamin M Neale §,2,3,5 , Jes Olesen §,59 , Daniel I Chasman §,21,38 , Dale R Nyholt §,78 , and Aarno Palotie §,1,2,3,4,5,9,79 .

1 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA. 2 Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, USA. 3 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA. 4 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK. 5 Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA. 6 FORMI, Oslo University Hospital, PO 4956 Nydalen, 0424 Oslo, Norway. 7 Department of Neurology, Oslo University Hospital, PO 4956 Nydalen, 0424 Oslo, Norway. 8 Institute of Clinical Medicine, University of Oslo, PO 1171 Blindern, 0318 Oslo, Norway. 9 Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. 10 Estonian Genome Center, University of Tartu, Tartu, Estonia. 11 Division of Endocrinology, Boston Children's Hospital, Boston, USA. 12 Statens Serum Institut, Dept of Epidemiology Research, Copenhagen, Denmark. 13 Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. 14 Illumina, 5200 Illumina Way, San Diego, USA. 15 Vall d'Hebron Research Institute, Pediatric Neurology, Barcelona, ​​Spain. 16 Folkhälsan Institute of Genetics, Helsinki, Finland, FI-00290. 17 Neuroscience Center, University of Helsinki, Helsinki, Finland, FI-00014. 18 Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland, FI-00014. 19 23andMe, Inc., 899 W. Evelyn Avenue, Mountain View, CA, USA. 20 Inserm Research Center for Epidemiology and Biostatistics (U897), University of Bordeaux, 33076 Bordeaux, France. 21 Division of Preventive Medicine, Brigham and Women's Hospital, Boston MA 02215. 22 deCODE Genetics, 101 Reykjavik, Iceland. 23 Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK. 24 VU University Amsterdam, Department of Biological Psychology, Amsterdam, the Netherlands, 1081 BT. 25 Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands, PO Box 9600, 2300 RC. 26 Department of Neurology, Helsinki University Central Hospital, Haartmaninkatu 4, 00290 Helsinki, Finland. 27 Institute for Stroke and Dementia Research, Hospital of the University of Munich, Ludwig-Maximilians-University Munich, Feodor-Lynen-Str. 17, 81377 Munich Germany. 28 Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen. 29 Karolinska Institutet, Department of Neuroscience, 171 77 Stockholm, Sweden. 30 Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD 4006, Australia. 31 Ulm University, Institute of Human Genetics, 89081 Ulm, Germany. 32 University of Oulu, Center for Life Course Epidemiology and Systems Medicine, Oulu, Finland, Box 5000, Fin-90014 University of Oulu. 33 Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. 34 Dept of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands, 3015 CN. 35 Dept of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands, 3015 CN. 36 Department of Clinical Chemistry, Fimlab Laboratories, and School of Medicine, University of Tampere, Tampere, Finland, 33520. 37 Department of Public Health, University of Helsinki, Helsinki, Finland. 38 Harvard Medical School, Boston MA 02115. 39 University Duisburg Essen, Essen, Germany. 40 Landspitali University Hospital, 101 Reykjavik, Iceland. 41 VU University Medical Center, Department of Psychiatry, Amsterdam, the Netherlands, 1081 HL. 42 Department of Psychiatry, Washington University School of Medicine, 660 South Euclid, CB 8134, St. Louis, MO 63110, USA. 43 University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 9700RB. 44 MRC Functional Genomics Unit, Department of Physiology, Anatomy & Genetics, Oxford University, UK. 45 Nuffield Department of Clinical Neuroscience, University of Oxford, UK. 46 Oxford Headache Centre, John Radcliffe Hospital, Oxford, UK. 47 Max Planck Institute of Psychiatry, Munich, Germany. 48 Christian Albrechts University, Kiel, Germany. 49 Institute of Human Genetics, Helmholtz Center Munich, Neuherberg, Germany. 50 Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki Finland. 51 National Institute for Health and Welfare, Helsinki, Finland. 52 Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland. 53 Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, USA 02115. 54 Dept of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands, 3015 CN. 55 Dept of Pain Management and Research, Oslo University Hospital, Oslo, 0424 Oslo, Norway. 56 Medical Faculty, University of Oslo, Oslo, 0318 Oslo, Norway. 57 Division of Mental Health, Norwegian Institute of Public Health, PO Box 4404 Nydalen, Oslo, Norway, NO-0403. 58 Kiel Pain and Headache Center, 24149 Kiel, Germany. 59 Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Denmark. 60 Institute of Biological Psychiatry, Mental Health Center Sct. Hans, University of Copenhagen, Roskilde, Denmark. 61 Institute Of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, DK-2100 Copenhagen, Denmark. 62 Institute of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark. 63 iPSYCH – The Lundbeck Foundation's Initiative for Integrative Psychiatric Research, DK-2100 Copenhagen, Denmark. 64 A list of members and affiliations appears in the Supplementary Note. 65 Department of Public Health, University of Helsinki, Helsinki, Finland. 66 Department of Health, National Institute for Health and Welfare, Helsinki, Finland. 67 Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, 20521. 68 Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, 20521. 69 Dept of Neurology, Erasmus University Medical Center, Rotterdam , the Netherlands, 3015 CN. 70 Imperial College London, Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE) Center for Environment and Health, School of Public Health, UK, W2 1PG. 71 University of Oulu, Biocenter Oulu, Finland, Box 5000, Fin-90014 University of Oulu. 72 Oulu University Hospital, Unit of Primary Care, Oulu, Finland, Box 10, Fin-90029 OYS. 73 University Medical Center Hamburg Eppendorf, Institute of Human Genetics, 20246 Hamburg, Germany. 74 Population Health Research Institute, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK. 75 Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. 76 Leiden University Medical Center, Department of Human Genetics, Leiden, The Netherlands, PO Box 9600, 2300 RC. 77 Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland. 78 Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, QLD 4059, Australia. 79 Department of Neurology, Massachusetts General Hospital, Boston, USA.