Genome-wide association analysis identifies susceptibility loci for migraine without aura

Tobias Freilinger; Verneri Anttila; Boukje De Vries; Rainer Malik; Mikko Kallela; Gisela M. Terwindt; Patricia Pozo-Rosich; Bendik Winsvold; Dale R. Nyholt; Willebrordus P.J. Van Oosterhout; Ville Artto; Unda Todt; Eija Hämäläinen; Jèssica Fernández-Morales; Mark A. Louter; Mari A. Kaunisto; Jean Schoenen; Olli Raitakari; Terho Lehtimäki; Marta Vila-Pueyo; Hartmut Göbel; Erich Wichmann; Cèlia Sintas; Andre G. Uitterlinden; Albert Hofman; Fernando Rivadeneira; Axel Heinze; Erling Tronvik; Cornelia M. Van Duijn; Jaakko Kaprio; Bru Cormand; Maija Wessman; Rune R. Frants; Thomas Meitinger; Bertram Müller-Myhsok; John Anker Zwart; Markus Färkkilä; Alfons MacAya; Michel D. Ferrari; Christian Kubisch; Aarno Palotie; Martin Dichgans; Arn M.J.M. Van Den Maagdenberg

doi:10.1038/ng.2307

Genome-wide association analysis identifies susceptibility loci for migraine without aura

Tobias Freilinger, Verneri Anttila, Boukje De Vries, Rainer Malik, Mikko Kallela, Gisela M. Terwindt, Patricia Pozo-Rosich, Bendik Winsvold, Dale R. Nyholt, Willebrordus P.J. Van Oosterhout, Ville Artto, Unda Todt, Eija Hämäläinen, Jèssica Fernández-Morales, Mark A. Louter, Mari A. Kaunisto, Jean Schoenen, Olli Raitakari, Terho Lehtimäki, Marta Vila-PueyoHartmut Göbel, Erich Wichmann, Cèlia Sintas, Andre G. Uitterlinden, Albert Hofman, Fernando Rivadeneira, Axel Heinze, Erling Tronvik, Cornelia M. Van Duijn, Jaakko Kaprio, Bru Cormand, Maija Wessman, Rune R. Frants, Thomas Meitinger, Bertram Müller-Myhsok, John Anker Zwart, Markus Färkkilä, Alfons MacAya, Michel D. Ferrari, Christian Kubisch, Aarno Palotie, Martin Dichgans, Arn M.J.M. Van Den Maagdenberg

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Abstract

Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 × 10-5 for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 × 10-4; combined P = 7.06 × 10-11) and at 3p24 (near TGFBR2; replication P = 1.0 × 10-4; combined P = 1.17 × 10-9). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 × 10-8 and P = 0.02; combined P = 3.86 × 10-8, respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder. © 2012 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	777-782
Journal	Nature Genetics
Volume	44
Issue number	7
DOIs	https://doi.org/10.1038/ng.2307
Publication status	Published - 1 Jul 2012

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Freilinger, T., Anttila, V., De Vries, B., Malik, R., Kallela, M., Terwindt, G. M., Pozo-Rosich, P., Winsvold, B., Nyholt, D. R., Van Oosterhout, W. P. J., Artto, V., Todt, U., Hämäläinen, E., Fernández-Morales, J., Louter, M. A., Kaunisto, M. A., Schoenen, J., Raitakari, O., Lehtimäki, T., ... Van Den Maagdenberg, A. M. J. M. (2012). Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nature Genetics, 44(7), 777-782. https://doi.org/10.1038/ng.2307

@article{f80cae35c1c34b35ab45cb4b898c3983,

title = "Genome-wide association analysis identifies susceptibility loci for migraine without aura",

abstract = "Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 × 10-5 for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 × 10-4; combined P = 7.06 × 10-11) and at 3p24 (near TGFBR2; replication P = 1.0 × 10-4; combined P = 1.17 × 10-9). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 × 10-8 and P = 0.02; combined P = 3.86 × 10-8, respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder. {\textcopyright} 2012 Nature America, Inc. All rights reserved.",

author = "Tobias Freilinger and Verneri Anttila and {De Vries}, Boukje and Rainer Malik and Mikko Kallela and Terwindt, {Gisela M.} and Patricia Pozo-Rosich and Bendik Winsvold and Nyholt, {Dale R.} and {Van Oosterhout}, {Willebrordus P.J.} and Ville Artto and Unda Todt and Eija H{\"a}m{\"a}l{\"a}inen and J{\`e}ssica Fern{\'a}ndez-Morales and Louter, {Mark A.} and Kaunisto, {Mari A.} and Jean Schoenen and Olli Raitakari and Terho Lehtim{\"a}ki and Marta Vila-Pueyo and Hartmut G{\"o}bel and Erich Wichmann and C{\`e}lia Sintas and Uitterlinden, {Andre G.} and Albert Hofman and Fernando Rivadeneira and Axel Heinze and Erling Tronvik and {Van Duijn}, {Cornelia M.} and Jaakko Kaprio and Bru Cormand and Maija Wessman and Frants, {Rune R.} and Thomas Meitinger and Bertram M{\"u}ller-Myhsok and Zwart, {John Anker} and Markus F{\"a}rkkil{\"a} and Alfons MacAya and Ferrari, {Michel D.} and Christian Kubisch and Aarno Palotie and Martin Dichgans and {Van Den Maagdenberg}, {Arn M.J.M.}",

year = "2012",

month = jul,

day = "1",

doi = "10.1038/ng.2307",

language = "English",

volume = "44",

pages = "777--782",

journal = "Nature Genetics",

issn = "1061-4036",

number = "7",

}

Freilinger, T, Anttila, V, De Vries, B, Malik, R, Kallela, M, Terwindt, GM, Pozo-Rosich, P, Winsvold, B, Nyholt, DR, Van Oosterhout, WPJ, Artto, V, Todt, U, Hämäläinen, E, Fernández-Morales, J, Louter, MA, Kaunisto, MA, Schoenen, J, Raitakari, O, Lehtimäki, T, Vila-Pueyo, M, Göbel, H, Wichmann, E, Sintas, C, Uitterlinden, AG, Hofman, A, Rivadeneira, F, Heinze, A, Tronvik, E, Van Duijn, CM, Kaprio, J, Cormand, B, Wessman, M, Frants, RR, Meitinger, T, Müller-Myhsok, B, Zwart, JA, Färkkilä, M, MacAya, A, Ferrari, MD, Kubisch, C, Palotie, A, Dichgans, M & Van Den Maagdenberg, AMJM 2012, 'Genome-wide association analysis identifies susceptibility loci for migraine without aura', Nature Genetics, vol. 44, no. 7, pp. 777-782. https://doi.org/10.1038/ng.2307

TY - JOUR

T1 - Genome-wide association analysis identifies susceptibility loci for migraine without aura

AU - Freilinger, Tobias

AU - Anttila, Verneri

AU - De Vries, Boukje

AU - Malik, Rainer

AU - Kallela, Mikko

AU - Terwindt, Gisela M.

AU - Pozo-Rosich, Patricia

AU - Winsvold, Bendik

AU - Nyholt, Dale R.

AU - Van Oosterhout, Willebrordus P.J.

AU - Artto, Ville

AU - Todt, Unda

AU - Hämäläinen, Eija

AU - Fernández-Morales, Jèssica

AU - Louter, Mark A.

AU - Kaunisto, Mari A.

AU - Schoenen, Jean

AU - Raitakari, Olli

AU - Lehtimäki, Terho

AU - Vila-Pueyo, Marta

AU - Göbel, Hartmut

AU - Wichmann, Erich

AU - Sintas, Cèlia

AU - Uitterlinden, Andre G.

AU - Hofman, Albert

AU - Rivadeneira, Fernando

AU - Heinze, Axel

AU - Tronvik, Erling

AU - Van Duijn, Cornelia M.

AU - Kaprio, Jaakko

AU - Cormand, Bru

AU - Wessman, Maija

AU - Frants, Rune R.

AU - Meitinger, Thomas

AU - Müller-Myhsok, Bertram

AU - Zwart, John Anker

AU - Färkkilä, Markus

AU - MacAya, Alfons

AU - Ferrari, Michel D.

AU - Kubisch, Christian

AU - Palotie, Aarno

AU - Dichgans, Martin

AU - Van Den Maagdenberg, Arn M.J.M.

PY - 2012/7/1

Y1 - 2012/7/1

N2 - Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 × 10-5 for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 × 10-4; combined P = 7.06 × 10-11) and at 3p24 (near TGFBR2; replication P = 1.0 × 10-4; combined P = 1.17 × 10-9). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 × 10-8 and P = 0.02; combined P = 3.86 × 10-8, respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder. © 2012 Nature America, Inc. All rights reserved.

AB - Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 × 10-5 for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 × 10-4; combined P = 7.06 × 10-11) and at 3p24 (near TGFBR2; replication P = 1.0 × 10-4; combined P = 1.17 × 10-9). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 × 10-8 and P = 0.02; combined P = 3.86 × 10-8, respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder. © 2012 Nature America, Inc. All rights reserved.

U2 - 10.1038/ng.2307

DO - 10.1038/ng.2307

M3 - Article

SN - 1061-4036

VL - 44

SP - 777

EP - 782

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -

Genome-wide association analysis identifies susceptibility loci for migraine without aura

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