Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
20802479
TITLE
Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1.
ABSTRACT
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 × 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 × 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 × 10⁻⁵, permuted threshold for genome-wide significance 7.7 × 10⁻⁵. To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.
DATE PUBLISHED
2010 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2010/03/01
accepted 2010/07/02
aheadofprint 2010/08/29
entrez 2010/08/31 06:00
pubmed 2010/08/31 06:00
medline 2010/10/29 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Anttila V Anttila Verneri V Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK. verneri.anttila@sanger.ac.uk
Stefansson H Stefansson Hreinn H
Kallela M Kallela Mikko M
Todt U Todt Unda U
Terwindt GM Terwindt Gisela M GM
Calafato MS Calafato M Stella MS
Nyholt DR Nyholt Dale R DR
Dimas AS Dimas Antigone S AS
Freilinger T Freilinger Tobias T
Müller-Myhsok B Müller-Myhsok Bertram B
Artto V Artto Ville V
Inouye M Inouye Michael M
Alakurtti K Alakurtti Kirsi K
Kaunisto MA Kaunisto Mari A MA
Hämäläinen E Hämäläinen Eija E
de Vries B de Vries Boukje B
Stam AH Stam Anine H AH
Weller CM Weller Claudia M CM
Heinze A Heinze Axel A
Heinze-Kuhn K Heinze-Kuhn Katja K
Goebel I Goebel Ingrid I
Borck G Borck Guntram G
Göbel H Göbel Hartmut H
Steinberg S Steinberg Stacy S
Wolf C Wolf Christiane C
Björnsson A Björnsson Asgeir A
Gudmundsson G Gudmundsson Gretar G
Kirchmann M Kirchmann Malene M
Hauge A Hauge Anne A
Werge T Werge Thomas T
Schoenen J Schoenen Jean J
Eriksson JG Eriksson Johan G JG
Hagen K Hagen Knut K
Stovner L Stovner Lars L
Wichmann HE Wichmann H-Erich HE
Meitinger T Meitinger Thomas T
Alexander M Alexander Michael M
Moebus S Moebus Susanne S
Schreiber S Schreiber Stefan S
Aulchenko YS Aulchenko Yurii S YS
Breteler MM Breteler Monique M B MM
Uitterlinden AG Uitterlinden Andre G AG
Hofman A Hofman Albert A
van Duijn CM van Duijn Cornelia M CM
Tikka-Kleemola P Tikka-Kleemola Päivi P
Vepsäläinen S Vepsäläinen Salli S
Lucae S Lucae Susanne S
Tozzi F Tozzi Federica F
Muglia P Muglia Pierandrea P
Barrett J Barrett Jeffrey J
Kaprio J Kaprio Jaakko J
Färkkilä M Färkkilä Markus M
Peltonen L Peltonen Leena L
Stefansson K Stefansson Kari K
Zwart JA Zwart John-Anker JA
Ferrari MD Ferrari Michel D MD
Olesen J Olesen Jes J
Daly M Daly Mark M
Wessman M Wessman Maija M
van den Maagdenberg AM van den Maagdenberg Arn M J M AM
Dichgans M Dichgans Martin M
Kubisch C Kubisch Christian C
Dermitzakis ET Dermitzakis Emmanouil T ET
Frants RR Frants Rune R RR
Palotie A Palotie Aarno A
International Headache Genetics Consortium
INVESTIGATORS
JOURNAL
VOLUME: 42
ISSUE: 10
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2010
MONTH: Oct
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
089062 Wellcome Trust United Kingdom
WT089062 Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Antigens, Surface genetics
Calcium-Binding Proteins genetics
Case-Control Studies genetics
Cell Adhesion Molecules genetics
Cells, Cultured genetics
Chromosomes, Human, Pair 8 genetics
Female genetics
Genetic Predisposition to Disease genetics
Genome, Human genetics
Genome-Wide Association Study genetics
Genotype genetics
Glutamate Carboxypeptidase II genetics
Humans genetics
Lymphocytes metabolism
Male metabolism
Microsatellite Repeats genetics
Migraine Disorders genetics
Quantitative Trait Loci genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Antigens, Surface
0 Calcium-Binding Proteins
0 Cell Adhesion Molecules
0 MTDH protein, human
EC 3.4.17.21 Glutamate Carboxypeptidase II
EC 3.4.17.21 glutamate carboxypeptidase II, human
OTHER ID's
OTHERID SOURCE
PMC2948563 NLM
UKMS31703 NLM
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