Abstract
Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 × 10−8 for rs6445055), two on chromosome 9 (P = 2.80 × 10−11 for rs2472493 near ABCA1 and P = 6.39 × 10−11 for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 10−11 for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.
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Acknowledgements
We gratefully acknowledge the contributions of all participants who volunteered within each cohort and the personnel responsible for the recruitment and administration of each study. We also thank the various funding sources that made this work possible. Complete funding information and acknowledgments can be found in the Supplementary Note.
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P.G.H., C.-Y.C., H.S., S.M., J.N.C.B. and R.W. performed analyses and drafted the manuscript. S.M., A.J.L., J.E.B.-W., V.V., L.R.P., N.P., C.D., A.V., D.A.M., J.E.C., J.L.W., C.M.v.D., C.J.H. and T.A. jointly conceived the project and supervised the work. P.G.H., H.S., R.W., A.N., A.W.H., A.M., C.V., R.H., G.T., B.A.O., S.-M.S., W.D.R., E.V., C.-C.K., D.D.G.D., J.L., J.L.H., Y.X.W., F.R., P.S.W., H.G.L., A.B.O., J.Z.L., B.W.F., R.C.W.W., T.Z., S.E.S., Y.-Y.T., G.C.-P., X.L., R.R.A., J.E.R., A.S., Y.Z., C.B., A.I.I., L.X., J.F.W., J.H.K., L.C.K., K.S., V.J., A.G.U., N.M.J., U.T., J.R.V., N.A., S.E., S.E.M., N.G.M., S.Y., E.-S.T., E.M.v.L., P.A., J.K., M.A.H., F.J., P.L., A.H., S.J.L., R.F., L.K., P.T.V.M.d.J., K.J.L., C.L.S., C.E.P., L.M.E.v.K., C.M., C.C.W.K., K.P.B., T.D.S., T.-Y.W., D.A.M., J.E.C. and A.B.S. were responsible for cohort-specific activities, data generation and analyses. T.L.Y. and K.S.S. were responsible for expression and eQTL work. P.G.H., C.-Y.C., H.S., S.M., T.-Y.W., D.A.M., J.L.W., C.M.v.D. and C.J.H. critically reviewed the manuscript.
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The authors declare competing financial interests. G.T., K.S. and U.T. are employees of deCODE Genetics/Amgen. C.D. has a consultant role for Laboratoires Théa, Novartis, Bausch+Lomb.
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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.
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Hysi, P., Cheng, CY., Springelkamp, H. et al. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma. Nat Genet 46, 1126–1130 (2014). https://doi.org/10.1038/ng.3087
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DOI: https://doi.org/10.1038/ng.3087
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