Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1.
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Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. / Anttila, Verneri; Stefansson, Hreinn; Kallela, Mikko; Todt, Unda; Terwindt, Gisela M; Calafato, M Stella; Nyholt, Dale R; Dimas, Antigone S; Freilinger, Tobias; Müller-Myhsok, Bertram; Artto, Ville; Inouye, Michael; Alakurtti, Kirsi; Kaunisto, Mari A; Hämäläinen, Eija; de Vries, Boukje; Stam, Anine H; Weller, Claudia M; Heinze, Axel; Heinze-Kuhn, Katja; Goebel, Ingrid; Borck, Guntram; Göbel, Hartmut; Steinberg, Stacy; Wolf, Christiane; Björnsson, Asgeir; Gudmundsson, Gretar; Kirchmann, Malene; Hauge, Anne; Werge, Thomas; Schoenen, Jean; Eriksson, Johan G; Hagen, Knut; Stovner, Lars; Wichmann, H-Erich; Meitinger, Thomas; Alexander, Michael; Moebus, Susanne; Schreiber, Stefan; Aulchenko, Yurii S; Breteler, Monique M B; Uitterlinden, Andre G; Hofman, Albert; Duijn, van; Cornelia, M; Tikka-Kleemola, Päivi; Vepsäläinen, Salli; Lucae, Susanne; Tozzi, Federica; Muglia, Pierandrea; Barrett, Jeffrey; Kaprio, Jaakko; Färkkilä, Markus; Peltonen, Leena; Stefansson, Kari; Zwart, John-Anker; Ferrari, Michel D; Olesen, Jes; Daly, Mark; Wessman, Maija; Maagdenberg, van den; Kubisch, Christian; Dichgans, Martin; Dermitzakis, Emmanouil T; Frants, Rune R; Palotie, Aarno; Consortium, International Headache Genetics.
In: NAT GENET, Vol. 42, No. 10, 10, 2010, p. 869-873.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1.
AU - Anttila, Verneri
AU - Stefansson, Hreinn
AU - Kallela, Mikko
AU - Todt, Unda
AU - Terwindt, Gisela M
AU - Calafato, M Stella
AU - Nyholt, Dale R
AU - Dimas, Antigone S
AU - Freilinger, Tobias
AU - Müller-Myhsok, Bertram
AU - Artto, Ville
AU - Inouye, Michael
AU - Alakurtti, Kirsi
AU - Kaunisto, Mari A
AU - Hämäläinen, Eija
AU - de Vries, Boukje
AU - Stam, Anine H
AU - Weller, Claudia M
AU - Heinze, Axel
AU - Heinze-Kuhn, Katja
AU - Goebel, Ingrid
AU - Borck, Guntram
AU - Göbel, Hartmut
AU - Steinberg, Stacy
AU - Wolf, Christiane
AU - Björnsson, Asgeir
AU - Gudmundsson, Gretar
AU - Kirchmann, Malene
AU - Hauge, Anne
AU - Werge, Thomas
AU - Schoenen, Jean
AU - Eriksson, Johan G
AU - Hagen, Knut
AU - Stovner, Lars
AU - Wichmann, H-Erich
AU - Meitinger, Thomas
AU - Alexander, Michael
AU - Moebus, Susanne
AU - Schreiber, Stefan
AU - Aulchenko, Yurii S
AU - Breteler, Monique M B
AU - Uitterlinden, Andre G
AU - Hofman, Albert
AU - Duijn, van
AU - Cornelia, M
AU - Tikka-Kleemola, Päivi
AU - Vepsäläinen, Salli
AU - Lucae, Susanne
AU - Tozzi, Federica
AU - Muglia, Pierandrea
AU - Barrett, Jeffrey
AU - Kaprio, Jaakko
AU - Färkkilä, Markus
AU - Peltonen, Leena
AU - Stefansson, Kari
AU - Zwart, John-Anker
AU - Ferrari, Michel D
AU - Olesen, Jes
AU - Daly, Mark
AU - Wessman, Maija
AU - Maagdenberg, van den
AU - Kubisch, Christian
AU - Dichgans, Martin
AU - Dermitzakis, Emmanouil T
AU - Frants, Rune R
AU - Palotie, Aarno
AU - Consortium, International Headache Genetics
PY - 2010
Y1 - 2010
N2 - 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??, 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??, permuted threshold for genome-wide significance 7.7 × 10??. To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.
AB - 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??, 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??, permuted threshold for genome-wide significance 7.7 × 10??. To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.
KW - Humans
KW - Male
KW - Female
KW - Genotype
KW - Cells, Cultured
KW - Case-Control Studies
KW - Quantitative Trait Loci
KW - Genome, Human
KW - Genetic Predisposition to Disease
KW - Microsatellite Repeats/genetics
KW - Genome-Wide Association Study
KW - Calcium-Binding Proteins/genetics
KW - Antigens, Surface/genetics
KW - Cell Adhesion Molecules/genetics
KW - Chromosomes, Human, Pair 8/genetics
KW - Glutamate Carboxypeptidase II/genetics
KW - Lymphocytes/metabolism
KW - Migraine Disorders/genetics
KW - Humans
KW - Male
KW - Female
KW - Genotype
KW - Cells, Cultured
KW - Case-Control Studies
KW - Quantitative Trait Loci
KW - Genome, Human
KW - Genetic Predisposition to Disease
KW - Microsatellite Repeats/genetics
KW - Genome-Wide Association Study
KW - Calcium-Binding Proteins/genetics
KW - Antigens, Surface/genetics
KW - Cell Adhesion Molecules/genetics
KW - Chromosomes, Human, Pair 8/genetics
KW - Glutamate Carboxypeptidase II/genetics
KW - Lymphocytes/metabolism
KW - Migraine Disorders/genetics
M3 - SCORING: Journal article
VL - 42
SP - 869
EP - 873
JO - NAT GENET
JF - NAT GENET
SN - 1061-4036
IS - 10
M1 - 10
ER -