Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1

V Anttila; H Stefansson; M Kallela; U Todt; GM Terwindt; MS Calafato; DR Nyholt; AS Dimas; T Freilinger; B Muller-Myhsok; V Artto; M Inouye; K Alakurtti; MA Kaunisto; E Hamalainen; B de Vries; AH Stam; CM Weller; A Heinze; K Heinze-Kuhn; I Goebel; G Borck; H Gobel; S Steinberg; C Wolf; A Bjornsson; G Gudmundsson; M Kirchmann; A Hauge; T Werge; J Schoenen; JG Eriksson; K Hagen; L Stovner; E Wichmann; T Meitinger; M Alexander; S Moebus; S Schreiber; YS Aulchenko; Monique Breteler; André Uitterlinden; Bert Hofman; Cornelia Duijn; P Tikka-Kleemola; null Vepsalainen; S Lucae; F Tozzi; P Muglia; J Barrett; J Kaprio; M Farkkila; L Peltonen; K Stefansson; JA Zwart; MD Ferrari; J Olesen; M Daly; M Wessman; AMJM Maagdenberg; M Dichgans; C Kubisch; ET Dermitzakis; RR Frants; A Palotie

doi:10.1038/ng.652

Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1

V Anttila, H Stefansson, M Kallela, U Todt, GM Terwindt, MS Calafato, DR Nyholt, AS Dimas, T Freilinger, B Muller-Myhsok, V Artto, M Inouye, K Alakurtti, MA Kaunisto, E Hamalainen, B de Vries, AH Stam, CM Weller, A Heinze, K Heinze-KuhnI Goebel, G Borck, H Gobel, S Steinberg, C Wolf, A Bjornsson, G Gudmundsson, M Kirchmann, A Hauge, T Werge, J Schoenen, JG Eriksson, K Hagen, L Stovner, E Wichmann, T Meitinger, M Alexander, S Moebus, S Schreiber, YS Aulchenko, Monique Breteler, André Uitterlinden, Bert Hofman, Cornelia Duijn, P Tikka-Kleemola, Vepsalainen, S Lucae, F Tozzi, P Muglia, J Barrett, J Kaprio, M Farkkila, L Peltonen, K Stefansson, JA Zwart, MD Ferrari, J Olesen, M Daly, M Wessman, AMJM Maagdenberg, M Dichgans, C Kubisch, ET Dermitzakis, RR Frants, A Palotie

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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.

Original language	Undefined/Unknown
Pages (from-to)	869-873
Number of pages	5
Journal	Nature Genetics
Volume	42
Issue number	10
DOIs	https://doi.org/10.1038/ng.652
Publication status	Published - 2010

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10.1038/ng.652

http://hdl.handle.net/1765/21304

Cite this

Anttila, V., Stefansson, H., Kallela, M., Todt, U., Terwindt, GM., Calafato, MS., Nyholt, DR., Dimas, AS., Freilinger, T., Muller-Myhsok, B., Artto, V., Inouye, M., Alakurtti, K., Kaunisto, MA., Hamalainen, E., de Vries, B., Stam, AH., Weller, CM., Heinze, A., ... Palotie, A. (2010). Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nature Genetics, 42(10), 869-873. https://doi.org/10.1038/ng.652

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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 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.",

author = "V Anttila and H Stefansson and M Kallela and U Todt and GM Terwindt and MS Calafato and DR Nyholt and AS Dimas and T Freilinger and B Muller-Myhsok and V Artto and M Inouye and K Alakurtti and MA Kaunisto and E Hamalainen and {de Vries}, B and AH Stam and CM Weller and A Heinze and K Heinze-Kuhn and I Goebel and G Borck and H Gobel and S Steinberg and C Wolf and A Bjornsson and G Gudmundsson and M Kirchmann and A Hauge and T Werge and J Schoenen and JG Eriksson and K Hagen and L Stovner and E Wichmann and T Meitinger and M Alexander and S Moebus and S Schreiber and YS Aulchenko and Monique Breteler and Andr{\'e} Uitterlinden and Bert Hofman and Cornelia Duijn and P Tikka-Kleemola and Vepsalainen and S Lucae and F Tozzi and P Muglia and J Barrett and J Kaprio and M Farkkila and L Peltonen and K Stefansson and JA Zwart and MD Ferrari and J Olesen and M Daly and M Wessman and AMJM Maagdenberg and M Dichgans and C Kubisch and ET Dermitzakis and RR Frants and A Palotie",

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doi = "10.1038/ng.652",

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Anttila, V, Stefansson, H, Kallela, M, Todt, U, Terwindt, GM, Calafato, MS, Nyholt, DR, Dimas, AS, Freilinger, T, Muller-Myhsok, B, Artto, V, Inouye, M, Alakurtti, K, Kaunisto, MA, Hamalainen, E, de Vries, B, Stam, AH, Weller, CM, Heinze, A, Heinze-Kuhn, K, Goebel, I, Borck, G, Gobel, H, Steinberg, S, Wolf, C, Bjornsson, A, Gudmundsson, G, Kirchmann, M, Hauge, A, Werge, T, Schoenen, J, Eriksson, JG, Hagen, K, Stovner, L, Wichmann, E, Meitinger, T, Alexander, M, Moebus, S, Schreiber, S, Aulchenko, YS, Breteler, M, Uitterlinden, A , Hofman, B, Duijn, C, Tikka-Kleemola, P, Vepsalainen, Lucae, S, Tozzi, F, Muglia, P, Barrett, J, Kaprio, J, Farkkila, M, Peltonen, L, Stefansson, K, Zwart, JA, Ferrari, MD, Olesen, J, Daly, M, Wessman, M, Maagdenberg, AMJM, Dichgans, M, Kubisch, C, Dermitzakis, ET, Frants, RR & Palotie, A 2010, 'Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1', Nature Genetics, vol. 42, no. 10, pp. 869-873. https://doi.org/10.1038/ng.652

TY - JOUR

T1 - Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1

AU - Anttila, V

AU - Stefansson, H

AU - Kallela, M

AU - Todt, U

AU - Terwindt, GM

AU - Calafato, MS

AU - Nyholt, DR

AU - Dimas, AS

AU - Freilinger, T

AU - Muller-Myhsok, B

AU - Artto, V

AU - Inouye, M

AU - Alakurtti, K

AU - Kaunisto, MA

AU - Hamalainen, E

AU - de Vries, B

AU - Stam, AH

AU - Weller, CM

AU - Heinze, A

AU - Heinze-Kuhn, K

AU - Goebel, I

AU - Borck, G

AU - Gobel, H

AU - Steinberg, S

AU - Wolf, C

AU - Bjornsson, A

AU - Gudmundsson, G

AU - Kirchmann, M

AU - Hauge, A

AU - Werge, T

AU - Schoenen, J

AU - Eriksson, JG

AU - Hagen, K

AU - Stovner, L

AU - Wichmann, E

AU - Meitinger, T

AU - Alexander, M

AU - Moebus, S

AU - Schreiber, S

AU - Aulchenko, YS

AU - Breteler, Monique

AU - Uitterlinden, André

AU - Hofman, Bert

AU - Duijn, Cornelia

AU - Tikka-Kleemola, P

AU - Vepsalainen, null

AU - Lucae, S

AU - Tozzi, F

AU - Muglia, P

AU - Barrett, J

AU - Kaprio, J

AU - Farkkila, M

AU - Peltonen, L

AU - Stefansson, K

AU - Zwart, JA

AU - Ferrari, MD

AU - Olesen, J

AU - Daly, M

AU - Wessman, M

AU - Maagdenberg, AMJM

AU - Dichgans, M

AU - Kubisch, C

AU - Dermitzakis, ET

AU - Frants, RR

AU - Palotie, A

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 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.

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 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.

U2 - 10.1038/ng.652

DO - 10.1038/ng.652

M3 - Article

C2 - 20802479

SN - 1061-4036

VL - 42

SP - 869

EP - 873

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -