Identification of genetic susceptibility loci for migraine

• Main Author: Anttila, Timo Verneri
• Other Authors: Geschwind, Dan, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Clinical Chemistry, University of Helsinki, Finland, Institute of Molecular Medicine, University of Helsinki, Finland (FIMM), Helsinki Biomedical Graduate School, University of Helsinki, Finland, Center of Excellence in Complex Disease Genetics, University of Helsinki, Finland, Wellcome Trust Sanger Institute, Cambridge, United Kingdom, Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, Palotie, Aarno, Wessman, Maija
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: Helsingin yliopisto 2010
• Subjects: perinnöllisyyslääketiede; Iceland
• Online Access: http://hdl.handle.net/10138/22649

Migraine is the common cause of chronic episodic headache, affecting 12%-15% of the Caucasian population (41 million Europeans and some half a million Finns), and causes considerable loss of quality of life to its sufferers, as well as being linked to increased risk for a wide range of conditions, from depression to stroke. Migraine is the 19th most severe disease in terms of disability-adjusted life years, and 9th among women. It is characterized by attacks of headache accompanied by sensitivity to external stimuli lasting 4-72 hours, and in a third of cases by neurological aura symptoms, such as loss of vision, speech or muscle function. The underlying pathophysiology, including what triggers migraine attacks and why they occur in the first place, is largely unknown. The aim of this study was to identify genetic factors associated with the hereditary susceptibility to migraine, in order to gain a better understanding of migraine mechanisms. In this thesis, we report the results of genetic linkage and association analyses on a Finnish migraine patient collection as well as migraineurs from Australia, Denmark, Germany, Iceland and the Netherlands. Altogether we studied genetic information of nearly 7,000 migraine patients and over 50,000 population-matched controls. We also developed a new migraine analysis method called the trait component analysis, which is based on individual patient responses instead of the clinical diagnosis. Using this method, we detected a number of new genetic loci for migraine, including on chromosome 17p13 (HLOD 4.65) and 10q22-q23 (female-specific HLOD 7.68) with significant evidence of linkage, along with five other loci (2p12, 8q12, 4q28-q31, 18q12-q22, and Xp22) detected with suggestive evidence of linkage. The 10q22-q23 locus was the first genetic finding in migraine to show linkage to the same locus and markers in multiple populations, with consistent detection in six different scans. Traditionally, ion channels have been thought to play a role in migraine susceptibility, but we ...