Journal
NATURE GENETICS
Volume 42, Issue 10, Pages 869-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.652
Keywords
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Funding
- Wellcome Trust [WT089062]
- Academy of Finland [200923, 00213]
- Helsinki University Central Hospital
- Academy of Finland Center of Excellence for Complex Disease Genetics
- EuroHead project [LSM-CT-2004-504837]
- Helsinki Biomedical Graduate School
- Finnish Cultural Foundation
- Finnish Neurology Foundation
- Biomedicum Helsinki Foundation
- Cambridge Biomedical Research Centre
- Australian National Health and Medical Research Council [339462, 613674]
- Australian Research Council [FT0991022]
- German Federal Ministry of Education and Research (BMBF) [01GS08121]
- German National Genome Research Network
- Center for Molecular Medicine Cologne
- Heinz Nixdorf Foundation
- Netherlands Organization for the Health Research and Development [90700217]
- Netherlands Organisation for Scientific Research (NWO) [918.56.602]
- Spinoza
- Center for Medical Systems Biology (CMSB) [050-060-409, 050-060-810, 175.010.2005.011, 911-03-012]
- National Center for Research Resources (US)
- Helmholtz Center Munich
- German Federal Ministry of Education and Research
- State of Bavaria
- Munich Center of Health Sciences (MC Health)
- Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (DG XII)
- Municipality of Rotterdam
- Deutsche Forschungsgemeinschaft
- Australian Research Council [FT0991022] Funding Source: Australian Research Council
- Academy of Finland (AKA) [200923, 200923] Funding Source: Academy of Finland (AKA)
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Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 x 10(-9), odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 x 10(-11) (odds ratio = 1.18, 95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 x 10(-5), permuted threshold for genome-wide significance 7.7 x 10(-5)). To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.
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