Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

Gormley, P., Anttila, V., Winsvold, B. S., Palta, P., Esko, T., Pers, T. H., Farh, K. H., Cuenca-Leon, E., Muona, M., Furlotte, N. A., Kurth, T., Ingason, A., McMahon, G., Ligthart, L., Terwindt, G. M., Kallela, M., Freilinger, T. M., Ran, C., Gordon, S. G., Stam, A. H., Steinberg, S., Borck, G., Koiranen, M., Quaye, L., Adams, H. H. H., Lehtimaki, T., Sarin, A. P., Wedenoja, J., Hinds, D. A., Buring, J. E., Schurks, M., Ridker, P. M., Hrafnsdottir, M. G., Stefansson, H., Ring, S. M., Hottenga, J. J., Penninx, Bwjh, Farkkila, M., Artto, V., Kaunisto, M., Vepsalainen, S., Malik, R., Heath, A. C., Madden, P. A. F., Martin, N. G., Montgomery, G. W., Kurki, M. I., Kals, M., Magi, R., Parn, K., Hamalainen, E., Huang, H. L., Byrnes, A. E., Franke, L., Huang, J., Stergiakouli, E., Lee, P. H., Sandor, C., Webber, C., Cader, Z., Muller-Myhsok, B., Schreiber, Stefan, Meitinger, T., Eriksson, J. G., Salomaa, V., Heikkila, K., Loehrer, E., Uitterlinden, A. G., Hofman, A., van Duijn, C. M., Cherkas, L., Pedersen, L. M., Stubhaug, A., Nielsen, C. S., Mannikko, M., Mihailov, E., Milani, L., Gobel, H., Esserlind, A. L., Christensen, A. F., Hansen, T. F., Werge, T., Kaprio, J., Aromaa, A. J., Raitakari, O., Ikram, M. A., Spector, T., Jarvelin, M. R., Metspalu, A., Kubisch, C., Strachan, D. P., Ferrari, M. D., Belin, A. C., Dichgans, M., Wessman, M., van den Maagdenberg, Amjm, Zwart, J. A., Boomsma, D. I., Smith, G. D. and Stefansson, K. (2016) Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine Nature Genetics, 48 (8). 856-+. DOI 10.1038/ng.3598.

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Abstract

Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association ( GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms ( SNPs) significantly associated with migraine risk ( P < 5 x 10(-8)) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.

Document Type: Article
Additional Information: Times Cited: 6 Gormley, Padhraig Anttila, Verneri Winsvold, Bendik S. Palta, Priit Esko, Tonu Pers, Tune H. Farh, Kai-How Cuenca-Leon, Ester Muona, Mikko Furlotte, Nicholas A. Kurth, Tobias Ingason, Andres McMahon, George Ligthart, Lannie Terwindt, Gisela M. Kallela, Mikko Freilinger, Tobias M. Ran, Caroline Gordon, Scott G. Stam, Anine H. Steinberg, Stacy Borck, Guntram Koiranen, Markku Quaye, Lydia Adams, Hieab H. H. Lehtimaki, Terho Sarin, Antti-Pekka Wedenoja, Juho Hinds, David A. Buring, Julie E. Schurks, Markus Ridker, Paul M. Hrafnsdottir, Maria Gudlaug Stefansson, Hreinn Ring, Susan M. Hottenga, Jouke-Jan Penninx, Brenda W. J. H. Farkkila, Markus Artto, Ville Kaunisto, Mari Vepsalainen, Salli Malik, Rainer Heath, Andrew C. Madden, Pamela A. F. Martin, Nicholas G. Montgomery, Grant W. Kurki, Mitja I. Kals, Mart Magi, Reedik Parn, Kalle Hamalainen, Eija Huang, Hailiang Byrnes, Andrea E. Franke, Lude Huang, Jie Stergiakouli, Evie Lee, Phil H. Sandor, Cynthia Webber, Caleb Cader, Zameel Muller-Myhsok, Bertram Schreiber, Stefan Meitinger, Thomas Eriksson, Johan G. Salomaa, Veikko Heikkila, Kauko Loehrer, Elizabeth Uitterlinden, Andre G. Hofman, Albert van Duijn, Cornelia M. Cherkas, Lynn Pedersen, Linda M. Stubhaug, Audun Nielsen, Christopher S. Mannikko, Minna Mihailov, Evelin Milani, Lili Gobel, Hartmut Esserlind, Ann-Louise Christensen, Anne Francke Hansen, Thomas Folkmann Werge, Thomas Kaprio, Jaakko Aromaa, Arpo J. Raitakari, Olli Ikram, M. Arfan Spector, Tim Jarvelin, Marjo-Riitta Metspalu, Andres Kubisch, Christian Strachan, David P. Ferrari, Michel D. Belin, Andrea C. Dichgans, Martin Wessman, Maija van den Maagdenberg, Arn M. J. M. Zwart, John-Anker Boomsma, Dorret I. Smith, George Davey Stefansson, Kari Eriksson, Nicholas Daly, Mark J. Neale, Benjamin M. Olesen, Jes Chasman, Daniel I. Nyholt, Dale R. Palotie, Aarno
Research affiliation: OceanRep > The Future Ocean - Cluster of Excellence
Kiel University
Refereed: Yes
DOI etc.: 10.1038/ng.3598
ISSN: 1061-4036
Projects: Future Ocean
Date Deposited: 14 Mar 2017 06:24
Last Modified: 19 Dec 2017 12:46
URI: http://eprints.uni-kiel.de/id/eprint/36111

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