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Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma


We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[A], odds ratio (OR) = 1.36, P = 5.0 × 10−10). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG.

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Figure 1: The 7q31 locus.


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We thank all the participants whose contribution made this study possible, as well as their ophthalmologists. We also thank the personnel at deCODE recruitment center and core facilities for their hard work and enthusiasm. We would also like to acknowledge A. Hill (University Hospitals of Leicester National Health Service (NHS) Trust) for invaluable help with sample collection and the Wellcome Trust for funding (programme grant 062346/Z/00/Z and project grant 078751/Z/05/Z). The authors acknowledge financial support from the UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. We also thank the following organizations for their financial support: Clifford Craig Medical Research Trust; Ophthalmic Research Institute of Australia; Pfizer Australia; Glaucoma Australia; American Health Assistance Foundation; the glaucoma research foundation and the Australian National Health and Medical Research Council (NHMRC); the International Glaucoma Association, UK and the Eire Glaucoma Society and Optegra UK Ltd. J.E.C. is supported in part by an NHMRC Practitioner Fellowship, and D.A.M. is a Pfizer Australia Research Fellow. We would also like to thank O. Wallerman, M. Jansson, L.-I. Larsson and L. Tomic for their assistance and the Swedish Research Council for financial support. The authors acknowledge the funding and support of the following organizations: the US National Institutes of Health (NIH)/National Eye Institute grant 1RO1EY018246 and the NIH Center for Inherited Diseases Research (CIDR) (PI: T. Young); the Verto Institute, the American Health Assistance Foundation (AHAF) National Glaucoma Research and the Ellison Foundation for Aging Research; and the Southampton Wellcome Trust Clinical Research Facility. We thank D.R. Nyholt, G. Montgomery, S. Medland, S. Gordon, A. Henders, B. McEvoy, M.J. Wright, M.J. Campbell and A. Caracella for obtaining funding for and processing the Australian genotype data. S.M. is supported by an Australian NHMRC Career Development Award.

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Authors and Affiliations



The study was designed, the results interpreted and the first draft written by G.T., U.T., F.J. and K.S. The statistical analysis was performed by G.T., A.W.H. and A.K. A. Jonasdottir, A.S. and S.A.G. did the bioinformatic analysis of the 7q31 region, A.H. did the phylogenetic analysis and G.M. did the imputation. Genotyping at deCODE genetics was supervised by G.B.W. and U.T. Those responsible for case and control ascertainment, recruitment and phenotype information were F.J., G.J.G., H.S., K.P.M., M.S.G. and O.S. (Icelandic POAG cases and controls); K.P.M. and K.T. (Icelandic myopia cases); L.S., M.A.A., R.C.T. and W.S.S.K. (Leicester POAG cases); D.A.C. and D.St.C. (controls used for Leicester cases); A. Jacob, A.J.C., A.J.L., A.M. J.G. and S.E. (Southampton POAG cases and controls); C.W. (Swedish POAG cases and controls); P.M., C.J.H., N.G.M., S.M., T.L.Y., A.W.H., J.E.C., K.P.B. and D.A.M. (Australian POAG cases and controls and collection, genotyping and analysis of the Australian Twin study); C.P.P., D.S.C.L., P.O.S.T., A.D.W., J.H. and M.Z. (collection and genotyping of Hong Kong and Shantou POAG cases and unaffected controls); and J.C.N.C. and N.T. (population controls from Hong Kong). All authors contributed to the final version of the paper.

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Correspondence to Gudmar Thorleifsson or Kari Stefansson.

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Competing interests

Authors whose affiliations are listed as deCODE Genetics are employees of deCODE Genetics, a biotechnology company. deCODE Genetics intends to incorporate the variants described in this paper into its genetic testing services.

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Supplementary Note, Supplementary Figures 1 and 2 and Supplmentary Tables 1–6. (PDF 407 kb)

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Thorleifsson, G., Walters, G., Hewitt, A. et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nat Genet 42, 906–909 (2010).

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