Anttila, Verneri ORCID: 0000-0002-0073-4675, Stefansson, Hreinn ORCID: 0000-0002-9331-6666, Kallela, Mikko, Todt, Unda, Terwindt, Gisela M., Calafato, M. Stella, Nyholt, Dale R., Dimas, Antigone S., Freilinger, Tobias, Mueller-Myhsok, Bertram, Artto, Ville, Inouye, Michael ORCID: 0000-0001-9413-6520, Alakurtti, Kirsi, Kaunisto, Mari A., Haemaelaeinen, Eija, de Vries, Boukje, Stam, Anine H., Weller, Claudia M., Heinze, Axel, Heinze-Kuhn, Katja, Goebel, Ingrid, Borck, Guntram, Goebel, Hartmut, Steinberg, Stacy, Wolf, Christiane, Bjoernsson, Asgeir, Gudmundsson, Gretar, Kirchmann, Malene, Hauge, Anne, Werge, Thomas, Schoenen, Jean, Eriksson, Johan G., Hagen, Knut, Stovner, Lars, Wichmann, Erich, Meitinger, Thomas ORCID: 0000-0002-8838-8403, Alexander, Michael, Moebus, Susanne, Schreiber, Stefan, Aulchenko, Yurii S., Breteler, Monique M. B., Uitterlinden, Andre G., Hofman, Albert, van Duijn, Cornelia M., Tikka-Kleemola, Paevi, Vepsaelaeinen, Salli, Lucae, Susanne, Tozzi, Federica ORCID: 0000-0002-3536-2920, Muglia, Pierandrea ORCID: 0000-0002-3973-8606, Barrett, Jeffrey, Kaprio, Jaakko ORCID: 0000-0002-3716-2455, Faerkkilae, Markus, Peltonen, Leena, Stefansson, Kari, Zwart, John-Anker, Ferrari, Michel D., Olesen, Jes ORCID: 0000-0002-6712-2702, Daly, Mark, Wessman, Maija, van den Maagdenberg, Arn M. J. M., Dichgans, Martin, Kubisch, Christian ORCID: 0000-0003-4220-0978, Dermitzakis, Emmanouil T., Frants, Rune R. and Palotie, Aarno (2010). Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nature Genet., 42 (10). S. 869 - 875. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-1718

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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 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Anttila, VerneriUNSPECIFIEDorcid.org/0000-0002-0073-4675UNSPECIFIED
Stefansson, HreinnUNSPECIFIEDorcid.org/0000-0002-9331-6666UNSPECIFIED
Kallela, MikkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Todt, UndaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Terwindt, Gisela M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Calafato, M. StellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nyholt, Dale R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dimas, Antigone S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freilinger, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller-Myhsok, BertramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Artto, VilleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Inouye, MichaelUNSPECIFIEDorcid.org/0000-0001-9413-6520UNSPECIFIED
Alakurtti, KirsiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaunisto, Mari A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haemaelaeinen, EijaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Vries, BoukjeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stam, Anine H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weller, Claudia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinze, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinze-Kuhn, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goebel, IngridUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borck, GuntramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goebel, HartmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinberg, StacyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bjoernsson, AsgeirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gudmundsson, GretarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirchmann, MaleneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauge, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Werge, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoenen, JeanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eriksson, Johan G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hagen, KnutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stovner, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wichmann, ErichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meitinger, ThomasUNSPECIFIEDorcid.org/0000-0002-8838-8403UNSPECIFIED
Alexander, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moebus, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schreiber, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aulchenko, Yurii S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Breteler, Monique M. B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uitterlinden, Andre G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofman, AlbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Duijn, Cornelia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tikka-Kleemola, PaeviUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vepsaelaeinen, SalliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lucae, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tozzi, FedericaUNSPECIFIEDorcid.org/0000-0002-3536-2920UNSPECIFIED
Muglia, PierandreaUNSPECIFIEDorcid.org/0000-0002-3973-8606UNSPECIFIED
Barrett, JeffreyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaprio, JaakkoUNSPECIFIEDorcid.org/0000-0002-3716-2455UNSPECIFIED
Faerkkilae, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peltonen, LeenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stefansson, KariUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zwart, John-AnkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferrari, Michel D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olesen, JesUNSPECIFIEDorcid.org/0000-0002-6712-2702UNSPECIFIED
Daly, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wessman, MaijaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van den Maagdenberg, Arn M. J. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dichgans, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kubisch, ChristianUNSPECIFIEDorcid.org/0000-0003-4220-0978UNSPECIFIED
Dermitzakis, Emmanouil T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frants, Rune R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palotie, AarnoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-496023
DOI: 10.1038/ng.652
Journal or Publication Title: Nature Genet.
Volume: 42
Number: 10
Page Range: S. 869 - 875
Date: 2010
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1546-1718
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FAMILIAL HEMIPLEGIC MIGRAINE; LYMPHOBLASTOID CELL-LINES; EPISODIC ATAXIA; SPREADING DEPRESSION; GENE-EXPRESSION; CONFERS RISK; GLUTAMATE; MUTATION; INVOLVEMENT; MECHANISMSMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/49602

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