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Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression


Craig, JE and Han, X and Qassim, A and Hassall, M and Cooke Bailey, JN and Kinzy, TG and Khawaja, AP and An, J and Marshall, H and Gharahkhani, P and Igo, RP and Graham, SL and Healey, PR and Ong, JS and Zhou, T and Siggs, O and Law, MH and Souzeau, E and Ridge, B and Hysi, PG and Burdon, KP and Mills, RA and Landers, J and Ruddle, JB and Agar, A and Galanopoulos, A and White, AJR and Willoughby, CE and Andrew, NH and Best, S and Vincent, AL and Goldberg, I and Radford-Smith, G and Martin, NG and Montgomery, GW and Vitart, V and Hoehn, R and Wojciechowski, R and Jonas, JB and Aung, T and Pasquale, LR and Cree, AJ and Sivaprasad, S and Vallabh, NA and Viswanathan, AC and Pasutto, F and Haines, JL and Klaver, CCW and van Duijn, CM and Casson, RJ and Foster, PJ and Khaw, PT and Hammond, CJ and Mackey, DA and Mitchell, P and Lotery, AJ and Wiggs, JL and Hewitt, AW and MacGregor, S, NEIGHBORHOOD consortium and UK Biobank Eye and Vision Consortium, Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression, Nature Genetics, 52, (2) pp. 160-166. ISSN 1061-4036 (2020) [Refereed Article]

Copyright Statement

Copyright 2020

DOI: doi:10.1038/s41588-019-0556-y


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.

Item Details

Item Type:Refereed Article
Keywords:glaucoma, polygenic risk
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
UTAS Author:Mackey, DA (Professor David Mackey)
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:144799
Year Published:2020
Web of Science® Times Cited:85
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-06-11
Last Modified:2022-08-29

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