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, G., Stam, A.H., Steinberg, S., Borck, G., Koiranen, M., Quaye, L., Adams, 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, B.W., Farkkila, M., Artto, V., Kaunisto, M., Vepsalainen, S., Malik, R., Heath, A.C., Madden, P.A., Martin, G., Montgomery, G.W., Hamalainen, E., Huang, H., Byrnes, A.E., Franke, L., Huang, J., Stergiakouli, E., Lee, P.H., Sandor, C., Webber, C., Cader, Z., Muller-Myhsok, B., Schreiber, S., 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, A.M., Zwart, J.-A., Boomsma, D.I., Smith, G.D., Stefansson, K., Eriksson, N., Daly, M.J., Neale, B.M., Olesen, J., Chasman, D.I., Nyholt, D.R., & Palotie, A. (2016) Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nature Genetics, 48(8), pp. 856-866.

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Migraine is a debilitating neurological disorder affecting around 1 in 7 people worldwide, but its molecular mechanisms remain poorly understood. Some debate exists over 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 performed the largest genetic study of migraine to date, comprising 59,674 cases and 316,078 controls from 22 GWA studies. We identified 45 independent single nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 x 10-8) that map to 38 distinct genomic loci, including 28 loci not previously reported and the first locus identified on chromosome X. Furthermore, a subset analysis for migraine without aura (MO) identified seven of the same loci as from the full sample, whereas no loci reached genome-wide significance in the migraine with aura (MA) subset. In subsequent computational analyzes, 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.

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ID Code: 91785
Item Type: Journal Article
Refereed: Yes
DOI: 10.1038/ng.3598
ISSN: 1546-1718
Divisions: Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2016 Nature America, Inc
Deposited On: 12 Jan 2016 04:08
Last Modified: 21 Oct 2016 01:53

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