Genome-wide meta-analysis identifies new susceptibility loci for migraine

Verneri Anttila and colleagues report meta-analysis of 29 genome-wide association studies for migraine. They identify five loci newly associated with migraine, three of which are associated with specific subtypes of migraine with or without aura. Migraine is the most common brain disorder, affecting...

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Published in:	Nature genetics Vol. 45; no. 8; pp. 912 - 917
Main Authors:	Anttila, Verneri, Winsvold, Bendik S, Gormley, Padhraig, Kurth, Tobias, Bettella, Francesco, McMahon, George, Kallela, Mikko, Malik, Rainer, de Vries, Boukje, Terwindt, Gisela, Medland, Sarah E, Todt, Unda, McArdle, Wendy L, Quaye, Lydia, Koiranen, Markku, Ikram, M Arfan, Lehtimäki, Terho, Stam, Anine H, Ligthart, Lannie, Wedenoja, Juho, Dunham, Ian, Neale, Benjamin M, Palta, Priit, Hamalainen, Eija, Schürks, Markus, Rose, Lynda M, Buring, Julie E, Ridker, Paul M, Steinberg, Stacy, Stefansson, Hreinn, Jakobsson, Finnbogi, Lawlor, Debbie A, Evans, David M, Ring, Susan M, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari A, Freilinger, Tobias, Schoenen, Jean, Frants, Rune R, Pelzer, Nadine, Weller, Claudia M, Zielman, Ronald, Heath, Andrew C, Madden, Pamela A F, Montgomery, Grant W, Martin, Nicholas G, Borck, Guntram, Göbel, Hartmut, Heinze, Axel, Heinze-Kuhn, Katja, Williams, Frances M K, Hartikainen, Anna-Liisa, Pouta, Anneli, van den Ende, Joyce, Uitterlinden, Andre G, Hofman, Albert, Amin, Najaf, Hottenga, Jouke-Jan, Vink, Jacqueline M, Heikkilä, Kauko, Alexander, Michael, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Wichmann, Heinz Erich, Aromaa, Arpo, Eriksson, Johan G, Traynor, Bryan J, Trabzuni, Daniah, Rossin, Elizabeth, Lage, Kasper, Jacobs, Suzanne B R, Gibbs, J Raphael, Birney, Ewan, Kaprio, Jaakko, Penninx, Brenda W, Boomsma, Dorret I, van Duijn, Cornelia, Raitakari, Olli, Jarvelin, Marjo-Riitta, Zwart, John-Anker, Cherkas, Lynn, Strachan, David P, Kubisch, Christian, Ferrari, Michel D, van den Maagdenberg, Arn M J M, Dichgans, Martin, Wessman, Maija, Smith, George Davey, Stefansson, Kari, Daly, Mark J
Format:	Journal Article Web Resource
Language:	English
Published:	New York Nature Publishing Group US 01-08-2013 Nature Publishing Group
Subjects:	631/208/205/2138 631/378 692/308/2056 Agriculture Analysis Animal Genetics and Genomics Biomedicine Cancer Research Cerebellum - metabolism Computational Biology Frontal Lobe - metabolism Gene Function Gene mapping Genetic aspects Genetic Loci Genetic Predisposition to Disease Genetic susceptibility Genetic variation Genome-Wide Association Study Genomes GWAS Headaches Human Genetics Human health sciences Humans letter Meta-analysis Migraine Migraine Disorders - genetics Neurologie Neurology Physiological aspects Polymorphism, Single Nucleotide Population Proteins Quantitative Trait Loci Risk factors Sciences de la santé humaine Signal transduction Studies United States United Kingdom Finland
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Summary:	Verneri Anttila and colleagues report meta-analysis of 29 genome-wide association studies for migraine. They identify five loci newly associated with migraine, three of which are associated with specific subtypes of migraine with or without aura. Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility ( P < 5 × 10 −8 ). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP , TBC1D7 , FUT9 , STAT6 and ATP5B .
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 info:eu-repo/grantAgreement/EC/FP7/602633 scopus-id:2-s2.0-84881022482 Conceived and designed the study: A.Palotie, D.C., D.R.N., V.Anttila, B.S.W., M.Daly, M.W., M.Dichgans, A.M., C.K., L.C., J.A.Z., M.R.J., C.D., D.I.B., J.K., T.K., M.Kallela, R.M., B.V., G.T., L.Q., M.A.I., L.L., E.H., M.S., H.S., K.S., F.J., T.F., B.M.M. Performed the experiments: V.Anttila, B.S.W., A.Palotie, D.R.N., G.D.S., M.W., M.Dichgans, A.M., C.K., J.A.Z., M.R.J., O.R., C.D., D.I.B., J.K., E.B., M.Kallela, B.V., G.T., E.H., T.F., R.R.F., N.G.M., A.G.U., T.M., J.G.E. Jointly supervised research: A.Palotie, D.C., D.R.N., M.Daly, K.S., G.D.S., M.W., M.Dichgans, A.M., M.Ferrari, C.K., T.K., D.S., L.C., J.A.Z., M.R.J., C.D., D.I.B., J.K., L.Q., G.T. Performed statistical analysis: V.Anttila, B.S.W., P.G., D.C., D.R.N., M.Daly, D.S., E.B., J.R.G., S.B.R.J., T.K., F.B., G.M., R.M., B.V., L.Q., M.A.I., L.L., I.D., P.P., M.S., S.Steinberg, T.F., B.M.M. Analysed the data: V.Anttila, B.S.W., P.G., A.Palotie, D.C., D.R.N., L.C., J.R.G., S.B.R.J., K.L., T.K., F.B., G.M., R.M., B.V., S.E.M., L.Q., M.A.I., L.L., J.W., P.P., M.S., S.Steinberg, H.S., T.F., N.A., B.M.M., D.T. All authors contributed to the final version of the manuscript. Wrote the paper: V.Anttila, B.S.W., A.Palotie, D.C., D.R.N., A.M., C.K. Details appear in the Supplementary Note. Author Contributions Contributed reagents/materials/analysis tools: D.C., D.R.N., M.Daly, A.Palotie, G.D.S., M.W., M.Dichgans, A.M., M.Ferrari, C.K., D.S., L.C., J.A.Z., M.R.J., O.R., C.D., D.I.B., B.W.P., J.K., E.B., J.R.G., K.L., E.R., V.Anttila, B.S.W., P.G., T.K., F.B., G.M., M.Kallela, R.M., B.V., G.T., U.T., W.L.M., L.Q., M.Koiranen, M.A.I., T.L., A.H.S., L.L., I.D., B.N., M.S., L.M.R., J.E.B., P.M.R., S.Steinberg, H.S., F.J., D.A.L., D.M.E., S.M.R., M.Färkkilä, V.Artto, M.A.K., T.F., J.S., R.R.F., N.P., C.M.W., R.Z., A.C.H., P.A.F.M., G.W.M., N.G.M., G.B., H.G., A.Heinze, K.H.K., F.M.K.W., A.L.H., A.Pouta, J.E., A.G.U., A.Hofman, J.J.H., J.M.V., K.H., M.A., B.M.M., S.Schreiber, T.M., E.W., A.A., J.G.E., B.T., D.T.
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/ng.2676