Abstract
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.
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Acknowledgements
Study-specific acknowledgments appear in the Supplementary Note. We wish to thank A. Coffey, S. Hunt, R. Gwillian, P. Whittaker, S. Potter and A. Tashakkori-Ghanbarian for their invaluable help with this study, and we collectively thank everyone who has contributed to the collection, genotyping and analysis of the individual cohorts, as well as all the study participants.
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A. Palotie, D.I.C., D.R.N., M.J.D., K.S., G.D.S., M.W., M.D., A.M.J.M.v.d.M., M.D.F., C.K., T.K., D.P.S., L.C., J.-A.Z., M.-R.J., C.v.D., D.I.B., J.K., L.Q. and G.T. jointly supervised research. A. Palotie, D.I.C., D.R.N., V. Anttila, B.S.W., M.J.D., M.W., M.D., A.M.J.M.v.d.M., C.K., L.C., J.-A.Z., M.-R.J., C.v.D., D.I.B., J.K., T.K., M. Kallela, R.M., B.d.V., G.T., L.Q., M.A.I., L.L., E.H., M.S., H.S., K.S., F.J., T.F. and B.M.-M. conceived and designed the study. V. Anttila, B.S.W., A. Palotie, D.R.N., G.D.S., M.W., M.D., A.M.J.M.v.d.M., C.K., J.-A.Z., M.-R.J., O.R., C.v.D., D.I.B., J.K., E.B., M. Kallela, B.d.V., G.T., E.H., T.F., R.R.F., N.G.M., A.G.U., T.M. and J.G.E. performed the experiments. V. Anttila, B.S.W., P.G., D.I.C., D.R.N., M.J.D., D.P.S., E.B., J.R.G., S.B.R.J., T.K., F.B., G.M., R.M., B.d.V., L.Q., M.A.I., L.L., I.D., P.P., M.S., S. Steinberg, T.F. and B.M.-M. performed statistical analysis. V. Anttila, B.S.W., P.G., A. Palotie, D.I.C., D.R.N., L.C., J.R.G., S.B.R.J., K.L., T.K., F.B., G.M., R.M., B.d.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. and D.T. analyzed the data. D.I.C., D.R.N., M.J.D., A. Palotie, G.D.S., M.W., M.D., A.M.J.M.v.d.M., M.D.F., C.K., D.P.S., L.C., J.-A.Z., M.-R.J., O.R., C.v.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.d.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.M.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.F., 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.v.d.E., A.G.U., A. Hofman, J.-J.H., J.M.V., K.H., M.A., B.M.-M., S. Schreiber, T.M., H.E.W., A.A., J.G.E., B.J.T. and D.T. contributed reagents and/or materials and/or analysis tools. V. Anttila, B.S.W., A. Palotie, D.I.C., D.R.N., A.M.J.M.v.d.M. and C.K. wrote the manuscript. All authors contributed to the final version of the manuscript.
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Anttila, V., Winsvold, B., Gormley, P. et al. Genome-wide meta-analysis identifies new susceptibility loci for migraine. Nat Genet 45, 912–917 (2013). https://doi.org/10.1038/ng.2676
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DOI: https://doi.org/10.1038/ng.2676
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