Abstract
Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.
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Change history
09 May 2013
In the version of this article initially published, the affiliations of Daniel W.H. Ho were incorrect, and the spelling of Sarayut Janmahasatian in the author list was incorrect. The errors have been corrected in the HTML and PDF versions of this article.
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Acknowledgements
We gratefully thank the invaluable contributions of all study participants, their relatives and staff at the recruitment centers. Complete funding information and acknowledgments by study can be found in the Supplementary Note.
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V.J.M.V., P.G.H., R.W., C.J.H., C.C.W.K., A.W.H., D.A.M., T.L.Y. and C.M.v.D. performed analyses and drafted the manuscript. C.C.W.K., D.S., C.J.H., J.E.B.-W., S.-M.S., C.M.v.D., A.H., D.A.M., S.M., A.D.P., V.V., C.W., P.N.B., T.-Y.W., J.S.R., T.L.Y., K.O., O. Pärssinen, S.P.Y., J.A.G., A. Metspalu, M.P., S.K.I. and N.P. jointly conceived the project and supervised the work. J.E.B.W., S.-M.S., D.A.M., T.L.Y., C.J.H., C.C.W.K., D.S., J.E.B.-W., C.M.v.D., R.W., P.G.H., V.J.M.V., K.O., Y.-Y.T., T.-Y.W., P.N.B., V.V., N.A., B.A.O., A.H., J.R.V., F.R., A.G.U., N.P., C.M., A. Mirshahi, T.Z., B.F., J.F.W., Z.V., O. Polasek, A.F.W., C.H., I.R., S.K.I., E.C., J.H.L., R.P.I., S.J., M.S., J.J.W., P.M., I.C., J.S.R., P.M.C., C.E.P., G.W.M., A. Mishra, W.A., F.M., M.P., L.C.K., T.D.S., E.Y.-D., A.N., O.R., C.-C.K., T.M., A.D., R.T.O., Y.Z., J.L., R.L., P.C., V.A.B., W.-T.T., E.V., T.A., E.-S.T., A. Metspalu, T.H., R.K., B.E.K.K., J.E.C., K.P.B., L.J.C., C.P.P., D.W.H.H., S.P.Y., J.W., O. Pärssinen, J.B.J., L.X., H.S.W., S.M.H., A.D.P., M.K., T.L., K.-M.M., C.L.S., C.W., N.J.T., D.M.E., B.S.P., J.P.K., G.M., G.H.S.B., M.K.I., X.Z., C.-Y.C., A.W.H., S.M., R.H., J.A.G. and Q.F. were responsible for study-specific data. G.H.S.B., V.J.M.V., Q.F. and J.A.G. were involved in the genetic risk score analysis. T.L.Y., A.A.B.B., T.G.M.F.G. and F.H. performed the data expression experiments. A.A.B.B., T.G.M.F.G., A.M. and S.M. were involved in pathway analyses. J.E.B.-W., S.-M.S., D.A.M., T.L.Y., K.O., T.-Y.W., P.N.B., T.G.M.F.G., S.K.I., E.C., J.J.W., A.J.M.H.V., C.-C.K., B.E.K.K., S.P.Y., C.W., N.J.T., G.H.S.B., M.K.I., A.W.H. and J.A.G. critically reviewed the manuscript.
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A full list of members appears in the Supplementary Note.
A full list of members appears in the Supplementary Note.
A full list of members appears in the Supplementary Note.
A full list of members appears in the Supplementary Note.
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Verhoeven, V., Hysi, P., Wojciechowski, R. et al. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. Nat Genet 45, 314–318 (2013). https://doi.org/10.1038/ng.2554
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DOI: https://doi.org/10.1038/ng.2554
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