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https://hdl.handle.net/2440/123608
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Type: | Journal article |
Title: | Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression |
Author: | Craig, J.E. Han, X. Qassim, A. Hassall, M. Cooke Bailey, J.N. Kinzy, T.G. Khawaja, A.P. An, J. Marshall, H. Gharahkhani, P. Igo, R.P. Graham, S.L. Healey, P.R. Ong, J.-S. Zhou, T. Siggs, O. Law, M.H. Souzeau, E. Ridge, B. Hysi, P.G. et al. |
Citation: | Nature Genetics, 2020; 52(2):160-166 |
Publisher: | Nature Research |
Issue Date: | 2020 |
ISSN: | 1061-4036 1546-1718 |
Statement of Responsibility: | Jamie E. Craig, Xikun Han ... Nicholas H (Nick) Andrew ... Robert J. Casson ... Anna Galanopoulos ... Mark M. Hassall ... et al. |
Abstract: | Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 × 10-6). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups. |
Keywords: | NEIGHBORHOOD consortium UK Biobank Eye and Vision Consortium Optic Nerve Humans Glaucoma Disease Progression Genetic Predisposition to Disease Glycoproteins Cytoskeletal Proteins Eye Proteins Trabeculectomy Odds Ratio Case-Control Studies Intraocular Pressure Multifactorial Inheritance Penetrance Polymorphism, Single Nucleotide United States Australia Genome-Wide Association Study United Kingdom |
Rights: | Cpyright status unknown |
DOI: | 10.1038/s41588-019-0556-y |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1107098 http://purl.org/au-research/grants/nhmrc/1116360 http://purl.org/au-research/grants/nhmrc/1023911 http://purl.org/au-research/grants/nhmrc/1116495 http://purl.org/au-research/grants/nhmrc/1147571 http://purl.org/au-research/grants/nhmrc/1150144 http://purl.org/au-research/grants/nhmrc/1063061 http://purl.org/au-research/grants/nhmrc/1154543 http://purl.org/au-research/grants/nhmrc/1154824 http://purl.org/au-research/grants/nhmrc/1059954 http://purl.org/au-research/grants/nhmrc/1154513 http://purl.org/au-research/grants/nhmrc/1103329 http://purl.org/au-research/grants/arc/FT130101902 |
Published version: | http://dx.doi.org/10.1038/s41588-019-0556-y |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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