Deep Ocular Phenotyping Across Primary Open-Angle Glaucoma Genetic Burden
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Published:2023-09-01
Issue:9
Volume:141
Page:891
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ISSN:2168-6165
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Container-title:JAMA Ophthalmology
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language:en
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Short-container-title:JAMA Ophthalmol
Author:
Sekimitsu Sayuri1, Xiang David23, Smith Sophie Lloyd1, Curran Katie4, Elze Tobias5, Friedman David S.2, Foster Paul J.6, Luo Yuyang27, Pasquale Louis R.8, Peto Tunde4, Segrè Ayellet V.27, Shweikh Yusrah9, Warwick Alasdair1011, Zhao Yan27, Wiggs Janey L.27, Zebardast Nazlee2, Allen Naomi12, Aslam Tariq12, Atan Denize12, Balaskas Konstantinos12, Barman Sarah12, Barrett Jenny12, Bishop Paul12, Black Graeme12, Braithwaite Tasanee12, Carare Roxana12, Chakravarthy Usha12, Chan Michelle12, Chua Sharon12, Day Alexander12, Desai Parul12, Dhillon Bal12, Dick Andrew12, Doney Alexander12, Egan Cathy12, Ennis Sarah12, Foster Paul12, Fruttiger Marcus12, Gallacher John12, Garway-Heath David12, Gibson Jane12, Guggenheim Jeremy12, Hammond Chris12, Hardcastle Alison12, Harding Simon12, Hogg Ruth12, Hysi Pirro12, Keane Pearse12, Khaw Peng Tee12, Khawaja Anthony12, Lascaratos Gerassimos12, Littlejohns Thomas12, Lotery Andrew12, Luben Robert12, Luthert Phil12, Macgillivray Tom12, Mackie Sarah12, Madhusudhan Savita12, Mcguinness Bernadette12, Mckay Gareth12, Mckibbin Martin12, Moore Tony12, Morgan James12, O'Sullivan Eoin12, Oram Richard12, Owen Chris12, Patel Praveen12, Paterson Euan12, Peto Tunde12, Petzold Axel12, Pontikos Nikolas12, Rahi Jugnoo12, Rudnicka Alicja12, Sattar Naveed12, Self Jay12, Sergouniotis Panagiotis12, Sivaprasad Sobha12, Steel David12, Stratton Irene12, Strouthidis Nicholas12, Sudlow Cathie12, Sun Zihan12, Tapp Robyn12, Thomas Dhanes12, Trucco Emanuele12, Tufail Adnan12, Viswanathan Ananth12, Vitart Veronique12, Weedon Mike12, Williams Katie12, Williams Cathy12, Woodside Jayne12, Yates Max12, Zheng Yalin12,
Affiliation:
1. Tufts University School of Medicine, Boston, Massachusetts 2. Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston 3. Harvard Medical School, Boston, Massachusetts 4. Centre for Public Health, Queen’s University Belfast, Belfast, United Kingdom 5. Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts 6. NIHR Biomedical Research Centre, Moorfields Eye Hospital & UCL Institute of Ophthalmology, London, United Kingdom 7. Ocular Genomics Institute, Harvard Medical School, Boston, Massachusetts 8. Icahn School of Medicine at Mount Sinai, Department of Ophthalmology, New York, New York 9. Sussex Eye Hospital, University Hospitals Sussex NHS Foundation Trust, Sussex, United Kingdom 10. University College London, Institute of Cardiovascular Science, London, United Kingdom 11. Medical Retina Service, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom 12. for the UK Biobank Eye and Vision Consortium
Abstract
ImportanceBetter understanding of primary open-angle glaucoma (POAG) genetics could enable timely screening and promote individualized disease risk prognostication.ObjectiveTo evaluate phenotypic features across genetic burden for POAG.Design, Setting, and ParticipantsThis 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.Main Outcomes and MeasuresPOAG prevalence based on structural coding, self-reports, and glaucoma-related traits.ResultsAmong 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).Conclusion and RelevanceResults 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.
Publisher
American Medical Association (AMA)
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