A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25 (original) (raw)
References
- Vitale, S., Ellwein, L., Cotch, M.F., Ferris, F.L. III & Sperduto, R. Prevalence of refractive error in the United States, 1999–2004. Arch. Ophthalmol. 126, 1111–1119 (2008).
Article Google Scholar - Morgan, I. & Rose, K. How genetic is school myopia? Prog. Retin. Eye Res. 24, 1–38 (2005).
Article Google Scholar - Wu, H.M. et al. Does education explain ethnic differences in myopia prevalence? A population-based study of young adult males in Singapore. Optom. Vis. Sci. 78, 234–239 (2001).
Article CAS Google Scholar - Rein, D.B. et al. The economic burden of major adult visual disorders in the United States. Arch. Ophthalmol. 124, 1754–1760 (2006).
Article Google Scholar - Bamashmus, M.A., Matlhaga, B. & Dutton, G.N. Causes of blindness and visual impairment in the West of Scotland. Eye 18, 257–261 (2004).
Article CAS Google Scholar - Evans, J.R., Fletcher, A.E. & Wormald, R.P. Causes of visual impairment in people aged 75 years and older in Britain: an add-on study to the MRC Trial of Assessment and Management of Older People in the Community. Br. J. Ophthalmol. 88, 365–370 (2004).
Article CAS Google Scholar - Resnikoff, S., Pascolini, D., Mariotti, S.P. & Pokharel, G.P. Global magnitude of visual impairment caused by uncorrected refractive errors in 2004. Bull. World Health Organ. 86, 63–70 (2008).
Article Google Scholar - Buch, H. et al. Prevalence and causes of visual impairment and blindness among 9980 Scandinavian adults: the Copenhagen City Eye Study. Ophthalmology 111, 53–61 (2004).
Article Google Scholar - Saw, S.M., Katz, J., Schein, O.D., Chew, S.J. & Chan, T.K. Epidemiology of myopia. Epidemiol. Rev. 18, 175–187 (1996).
Article CAS Google Scholar - Rose, K.A. et al. Outdoor activity reduces the prevalence of myopia in children. Ophthalmology 115, 1279–1285 (2008).
Article Google Scholar - Lopes, M.C., Andrew, T., Carbonaro, F., Spector, T.D. & Hammond, C.J. Estimating heritability and shared environmental effects for refractive error in twin and family studies. Invest. Ophthalmol. Vis. Sci. 50, 126–131 (2009).
Article Google Scholar - Vitale, S., Sperduto, R.D. & Ferris, F.L. III. Increased prevalence of myopia in the United States between 1971–1972 and 1999–2004. Arch. Ophthalmol. 127, 1632–1639 (2009).
Article Google Scholar - Zippel, R. et al. Ras-GRF, the activator of Ras, is expressed preferentially in mature neurons of the central nervous system. Brain Res. Mol. Brain Res. 48, 140–144 (1997).
Article CAS Google Scholar - Raaijmakers, J.H. & Bos, J.L. Specificity in Ras and Rap signaling. J. Biol. Chem. 284, 10995–10999 (2009).
Article CAS Google Scholar - de la Puente, A. et al. Structural characterization of Rasgrf1 and a novel linked imprinted locus. Gene 291, 287–297 (2002).
Article CAS Google Scholar - Yoon, B.J. et al. Regulation of DNA methylation of Rasgrf1. Nat. Genet. 30, 92–96 (2002).
Article CAS Google Scholar - Mattingly, R.R. & Macara, I.G. Phosphorylation-dependent activation of the Ras-GRF/CDC25Mm exchange factor by muscarinic receptors and G-protein beta gamma subunits. Nature 382, 268–272 (1996).
Article CAS Google Scholar - Tonini, R. et al. Expression of Ras-GRF in the SK-N-BE neuroblastoma accelerates retinoic-acid-induced neuronal differentiation and increases the functional expression of the IRK1 potassium channel. Eur. J. Neurosci. 11, 959–966 (1999).
Article CAS Google Scholar - Tigges, M. et al. Effects of muscarinic cholinergic receptor antagonists on postnatal eye growth of rhesus monkeys. Optom. Vis. Sci. 76, 397–407 (1999).
Article CAS Google Scholar - Tong, L. et al. Atropine for the treatment of childhood myopia: effect on myopia progression after cessation of atropine. Ophthalmology 116, 572–579 (2009).
Article Google Scholar - Mertz, J.R. & Wallman, J. Choroidal retinoic acid synthesis: a possible mediator between refractive error and compensatory eye growth. Exp. Eye Res. 70, 519–527 (2000).
Article CAS Google Scholar - Brambilla, R. et al. A role for the Ras signalling pathway in synaptic transmission and long-term memory. Nature 390, 281–286 (1997).
Article CAS Google Scholar - Fernández-Medarde, A. et al. RasGRF1 disruption causes retinal photoreception defects and associated transcriptomic alterations. J. Neurochem. 110, 641–652 (2009).
Article Google Scholar - Schmucker, C. & Schaeffel, F. In vivo biometry in the mouse eye with low coherence interferometry. Vision Res. 44, 2445–2456 (2004).
Article Google Scholar - Zhou, X. et al. The development of the refractive status and ocular growth in C57BL/6 mice. Invest. Ophthalmol. Vis. Sci. 49, 5208–5214 (2008).
Article Google Scholar - Solouki, A. et al. A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q14. Nat. Genet. advance online publication, doi:10.1038/ng.663 (12 September 2010).
- Deans, M.R., Volgyi, B., Goodenough, D.A., Bloomfield, S.A. & Paul, D.L. Connexin36 is essential for transmission of rod-mediated visual signals in the mammalian retina. Neuron 36, 703–712 (2002).
Article CAS Google Scholar - Wallman, J. & Winawer, J. Homeostasis of eye growth and the question of myopia. Neuron 43, 447–468 (2004).
Article CAS Google Scholar - Font de Mora, J. et al. Ras-GRF1 signaling is required for normal beta-cell development and glucose homeostasis. EMBO J. 22, 3039–3049 (2003).
Article CAS Google Scholar
Acknowledgements
The King's College London authors acknowledge funding from the Wellcome Trust, the European Union MyEuropia Marie Curie Research Training Network, Guide Dogs for the Blind Association, the European Community's FP7 (HEALTH-F2-2008-201865-GEFOS), European Network of Genetic and Genomic Epidemiology (ENGAGE) (HEALTH-F4-2007-201413), the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254), US National Institutes of Health (NIH)/National Eye Institute (NEI) grant 1RO1EY018246 and genotyping by the NIH Center for Inherited Disease Research. The study also received support from the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service Foundation Trust partnering with King's College London. We are grateful to the volunteer twins, C. Smoliner and M. Liew, and to R. Metlapally and Felicia Hawthorne in T.L.Y.'s laboratory for RASGRF1 expression studies.
The Rotterdam Study acknowledges Netherlands Organisation of Scientific Research (NWO); the Erasmus Medical Center; Netherlands Organization for the Health Research and Development (ZonMw); UitZicht; Research Institute for Diseases in the Elderly (RIDE); the European Commission Directorate-General XII; the Municipality of Rotterdam; Netherlands Genomics Initiative (NGI); Lijf en Leven; MD Fonds; Henkes; Oogfonds; Stichting Wetenschappelijk Onderzoek Het Oogziekenhuis (SWOO); Swart van Essen; Bevordering van Volkskracht; Blindenhulp; Landelijke Stichting voor Blinden en Slechtzienden (LSBS); Rotterdamse Vereniging voor Blindenbelangen; OOG Foundation; Algemene Nederlandse Vereniging ter Voorkoming van Blindheid (ANVVB); Rotterdam Eye Institute (REI); Laméris Ootech BV; Topcon BV; Heidelberg Engineering; A. Hooghart, C. Brussee, R. Bernaerts-Biskop, P. van Hilten, P. Arp, M. Jhamai, M. Moorhouse, J. Vergeer, M. Verkerk, S. Bervoets and P. van der Spek. E.S., A.F.-M. and L.M. were supported by grants from Instituto de Salud Carlos III (ISCIII) (FIS PS09/01979) and Junta de Castilla y León (JcyL) (SA044A08 and GR93) and received institutional support from Red Temática de Investigación Cooperativa en Cáncer (RTICC) (RD06/0020/000), ISCIII, Spain.
The Australian group acknowledges the National Health and Medical Research Council (NHMRC) for the Australian Twin Registry (ATR) Enabling Grant, Project Grant 350415, Medical Genomics Grant, and the Genetic Cluster Computer (NWO 480-05-003), Clifford Craig Medical Research Trust, Ophthalmic Research Institute of Australia (ORIA), American Health Assistance Foundation (AHAF), Peggy and Leslie Cranbourne Foundation, Foundation for Children and Jack Brockhoff Foundation.
The 1958 British Birth Cohort was funded for biomedical assessment (Medical Research Council), for the GWAS (Wellcome Trust 083478) and analysis at Great Ormond Street Hospital/University College London (UCL). Institute of Child Health and Moorfields Eye Hospital/Institute of Ophthalmology, UCL were each part-funded by NIHR Biomedical Research Centres awards.
Additional acknowledgements are contained within the Supplementary Note.
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Author notes
- Pirro G Hysi and Terri L Young: These authors contributed equally to this work.
Authors and Affiliations
- Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, UK
Pirro G Hysi, Toby Andrew, Margarida C Lopes, Francis Carbonaro, Samantha J Fahy, Timothy D Spector & Christopher J Hammond - Center for Human Genetics, Duke University, Durham, North Carolina, USA
Terri L Young & Yi-Ju Li - Lions Eye Institute, University of Western Australia, Centre for Ophthalmology and Visual Science, Perth, Australia
David A Mackey - Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia
David A Mackey & Alex W Hewitt - University of Salamanca, CIC-IBMCC (CSIC-USAL), Salamanca, Spain
Alberto Fernández-Medarde, Lara Manyes, Angel Porteros & Eugenio Santos - Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands
Abbas M Solouki, Johannes R Vingerling & Caroline C W Klaver - Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
Abbas M Solouki, Johannes R Vingerling, M Kamran Ikram, Cornelia M van Duijn & Caroline C W Klaver - Genetics and Population Health, Queensland Institute of Medical Research, Brisbane, Australia
Stuart Macgregor & Nicholas G Martin - Department of Psychiatry, University of Hong Kong, Hong Kong, China
Lee Yiu Fai & Pak C Sham - Medical Research Council Center for Epidemiology for Child Health, Institute of Child Health, University College London, London, UK
Jugnoo S Rahi
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Contributions
T.L.Y., D.A.M., T.A. and C.J.H. jointly conceived the project and supervised the work. S.M., Y.J.-L., L.Y.F., P.C.S., N.G.M., P.G.H. and A.M.S. helped with the data analyses. A.F.-M., L.M., A.P. and E.S. performed the animal experiments. A.W.H., J.R.V., M.K.I., C.M.v.D., T.D.S., J.S.R. and C.C.W.K. supervised cohort recruitment, genotyping and analysis in replication cohorts. F.C., S.J.F. and M.C.L. contributed during subject and data collection.
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Correspondence toChristopher J Hammond.
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Hysi, P., Young, T., Mackey, D. et al. A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25.Nat Genet 42, 902–905 (2010). https://doi.org/10.1038/ng.664
- Received: 02 February 2010
- Accepted: 19 August 2010
- Published: 12 September 2010
- Issue Date: October 2010
- DOI: https://doi.org/10.1038/ng.664