Journal
NATURE GENETICS
Volume 52, Issue 2, Pages 160-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41588-019-0556-y
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Funding
- Welsh Assembly Government
- British Heart Foundation
- Diabetes UK
- National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital and the UCL Institute of Ophthalmology
- Fight for Sight charity
- Moorfields Eye Charity
- Macular Society
- International Glaucoma Association
- Alcon Research Institute
- National Health and Medical Research Council (NHMRC) of Australia [1107098, 1116360, 1116495, 1023911, 1150144, 1147571]
- Ophthalmic Research Institute of Australia
- BrightFocus Foundation
- UK and Eire Glaucoma Society
- Royal Liverpool University Hospital
- NHMRC [APP1154543, APP1154824, APP1059954, APP1154513, APP1103329, 1063061]
- Australian Research Council [FT130101902]
- National Institutes of Health [R01 EY015473, P30 EY014104, R01 EY022305]
- University of Queensland
- Queensland Institute of Medical Research Berghofer PhD Top Up Scholarship
- MRC [MC_UU_00007/10, MC_PC_12028] Funding Source: UKRI
- Australian Research Council [FT130101902] Funding Source: Australian Research Council
- National Health and Medical Research Council of Australia [1150144, 1107098, 1063061, 1147571] Funding Source: NHMRC
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Multitrait genome-wide analysis of glaucoma and related phenotypes identifies new risk loci and enables development of a polygenic risk score to predict disease susceptibility and key clinical outcomes. 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 x 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.
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