| Title: | Deep Ocular Phenotyping Across Primary Open-Angle Glaucoma Genetic Burden |
| Journal: | JAMA Ophthalmology |
| Published: | 1 Sep 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37589995/ |
| DOI: | https://doi.org/10.1001/jamaophthalmol.2023.3645 |
| URL: | https://discovery.ucl.ac.uk/10176138/1/Foster_POAG_PRS_Manuscript_vClean.pdf |
Publication 9664
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Abstract
Importance: Better understanding of primary open-angle glaucoma (POAG) genetics could enable timely screening and promote individualized disease risk prognostication.</p>
Objective: To evaluate phenotypic features across genetic burden for POAG.</p>
Design, Setting, and Participants: This was a cross-sectional, population-based study conducted from 2006 to 2010. Included participants were individuals from the UK Biobank aged 40 to 69 years. Individuals with non-POAG forms of glaucoma were excluded from the analysis. Data were statistically analyzed from October 2022 to January 2023.</p>
Main Outcomes and Measures: POAG prevalence based on structural coding, self-reports, and glaucoma-related traits.</p>
Results: Among 407 667 participants (mean [SD] age, 56.3 [8.1] years; 219 183 majority sex [53.8%]) were 14 171 POAG cases. Area under receiver operating characteristic curve for POAG detection was 0.748 in a model including polygenic risk score (PRS), age, sex, and ancestry. POAG prevalence in the highest decile of PRS was 7.4% (3005 of 40 644) vs 1.3% (544 of 40 795) in lowest decile (P < .001). A 1-SD increase in PRS was associated with 1.74 times higher odds of POAG (95% CI, 1.71-1.77), a 0.61-mm Hg increase in corneal-compensated intraocular pressure (IOP; 95% CI, 0.59-0.64), a -0.09-mm Hg decrease in corneal hysteresis (95% CI, -0.10 to -0.08), a 0.08-mm Hg increase in corneal resistance factor (95% CI, 0.06-0.09), and a -0.08-diopter decrease in spherical equivalent (95% CI, -0.11 to -0.07; P < .001 for all). A 1-SD increase in PRS was associated with a thinning of the macula-region retinal nerve fiber layer (mRNFL) of 0.14 μm and macular ganglion cell complex (GCC) of 0.26 μm (P < .001 for both). In the subset of individuals with fundus photographs, a 1-SD increase in PRS was associated with 1.42 times higher odds of suspicious optic disc features (95% CI, 1.19-1.69) and a 0.013 increase in cup-disc ratio (CDR; 95% CI, 0.012-0.014; P < .001 for both). A total of 22 of 5193 fundus photographs (0.4%) in decile 10 had disc hemorrhages, and 27 of 5257 (0.5%) had suspicious optic disc features compared with 9 of 5158 (0.2%) and 10 of 5219 (0.2%), respectively, in decile 1 (P < .001 for both). CDR in decile 10 was 0.46 compared with 0.41 in decile 1 (P < .001).</p>
Conclusion and Relevance: Results suggest that PRS identified a group of individuals at substantially higher risk for POAG. Higher genetic risk was associated with more advanced disease, namely higher CDR and corneal-compensated IOP, thinner mRNFL, and thinner GCC. Associations with POAG PRS and corneal hysteresis and greater prevalence of disc hemorrhages were identified. These results suggest that genetic risk is an increasingly important parameter for risk stratification to consider in clinical practice.</p>
94 Authors
- Sayuri Sekimitsu
- David Xiang
- Sophie Lloyd Smith
- Katie Curran
- Tobias Elze
- David S. Friedman
- Paul J. Foster
- Yuyang Luo
- Louis R. Pasquale
- Tunde Peto
- Ayellet V. Segrè
- Yusrah Shweikh
- Alasdair Warwick
- Yan Zhao
- Janey L. Wiggs
- Nazlee Zebardast
- Naomi Allen
- Tariq Aslam
- Denize Atan
- Konstantinos Balaskas
- Sarah Barman
- Jenny Barrett
- Paul Bishop
- Graeme Black
- Tasanee Braithwaite
- Roxana Carare
- Usha Chakravarthy
- Michelle Chan
- Sharon Chua
- Alexander Day
- Parul Desai
- Bal Dhillon
- Andrew Dick
- Alexander Doney
- Cathy Egan
- Sarah Ennis
- Paul Foster
- Marcus Fruttiger
- John Gallacher
- David Garway-Heath
- Jane Gibson
- Jeremy Guggenheim
- Chris Hammond
- Alison Hardcastle
- Simon Harding
- Ruth Hogg
- Pirro Hysi
- Pearse Keane
- Peng Tee Khaw
- Anthony Khawaja
- Gerassimos Lascaratos
- Thomas Littlejohns
- Andrew Lotery
- Robert Luben
- Phil Luthert
- Tom Macgillivray
- Sarah Mackie
- Savita Madhusudhan
- Bernadette Mcguinness
- Gareth Mckay
- Martin Mckibbin
- Tony Moore
- James Morgan
- Eoin O'Sullivan
- Richard Oram
- Chris Owen
- Praveen Patel
- Euan Paterson
- Tunde Peto
- Axel Petzold
- Nikolas Pontikos
- Jugnoo Rahi
- Alicja Rudnicka
- Naveed Sattar
- Jay Self
- Panagiotis Sergouniotis
- Sobha Sivaprasad
- David Steel
- Irene Stratton
- Nicholas Strouthidis
- Cathie Sudlow
- Zihan Sun
- Robyn Tapp
- Dhanes Thomas
- Emanuele Trucco
- Adnan Tufail
- Ananth Viswanathan
- Veronique Vitart
- Mike Weedon
- Katie Williams
- Cathy Williams
- Jayne Woodside
- Max Yates
- Yalin Zheng
1 Application
| Application ID | Title |
|---|---|
| 50211 | Uncovering genetic and biological causes of ocular diseases and traits through integrative analysis of genetic, functional genomic, clinical, and ocular imaging data |
Enabling scientific discoveries that improve human health