| Title: | A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration |
| Journal: | EBioMedicine |
| Published: | 11 Apr 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37055258/ |
| DOI: | https://doi.org/10.1016/j.ebiom.2023.104551 |
| URL: | http://www.thelancet.com/article/S2352396423001160/pdf |
Publication 11325
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Abstract
BACKGROUND: High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER.</p>
METHODS: The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression.</p>
FINDINGS: In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17-21%), 2% (1-3%), 8% (7-10%) and 6% (3-9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75-0.81), 0.58 (0.53-0.64), 0.71 (0.69-0.74) and 0.67 (0.62-0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92-1.24).</p>
INTERPRETATION: Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted for.</p>
FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201).</p>
183 Authors
- Rosie Clark
- Samantha Sze-Yee Lee
- Ran Du
- Yining Wang
- Sander C.M. Kneepkens
- Jason Charng
- Yu Huang
- Michael L. Hunter
- Chen Jiang
- J.Willem L. Tideman
- Ronald B. Melles
- Caroline C.W. Klaver
- David A. Mackey
- Cathy Williams
- Hélène Choquet
- Kyoko Ohno-Matsui
- Jeremy A. Guggenheim
- Joan E. Bailey-Wilson
- Paul N. Baird
- Veluchamy A. Barathi
- Ginevra Biino
- Kathryn P. Burdon
- Harry Campbell
- Li Jia Chen
- Ching-Yu Cheng
- Emily Y. Chew
- Jamie E. Craig
- Margaret M. Deangelis
- Cécile Delcourt
- Xiaohu Ding
- Qiao Fan
- Maurizio Fossarello
- Paul J. Foster
- Puya Gharahkhani
- Jeremy A. Guggenheim
- Xiaobo Guo
- Annechien E.G. Haarman
- Toomas Haller
- Christopher J. Hammond
- Xikun Han
- Caroline Hayward
- Mingguang He
- Alex W. Hewitt
- Quan Hoang
- Pirro G. Hysi
- Adriana I. Iglesias
- Robert P. Igo
- Sudha K. Iyengar
- Jost B. Jonas
- Mika Kähönen
- Jaakko Kaprio
- Anthony P. Khawaja
- Barbara E. Klein
- Jonathan H. Lass
- Kris Lee
- Terho Lehtimäki
- Deyana Lewis
- Qing Li
- Shi-Ming Li
- Leo-Pekka Lyytikäinen
- Stuart MacGregor
- David A. Mackey
- Nicholas G. Martin
- Akira Meguro
- Andres Metspalu
- Candace Middlebrooks
- Masahiro Miyake
- Nobuhisa Mizuki
- Anthony Musolf
- Stefan Nickels
- Konrad Oexle
- Chi Pui Pang
- Olavi Pärssinen
- Andrew D. Paterson
- Norbert Pfeiffer
- Ozren Polasek
- Jugnoo S. Rahi
- Olli Raitakari
- Igor Rudan
- Srujana Sahebjada
- Seang-Mei Saw
- Claire L. Simpson
- Dwight Stambolian
- E-Shyong Tai
- Milly S. Tedja
- J. Willem L. Tideman
- Akitaka Tsujikawa
- Cornelia M. van Duijn
- Virginie J.M. Verhoeven
- Veronique Vitart
- Ningli Wang
- Ya Xing Wang
- Juho Wedenoja
- Wen Bin Wei
- Cathy Williams
- Katie M. Williams
- James F. Wilson
- Robert Wojciechowski
- Jason C.S. Yam
- Kenji Yamashiro
- Maurice K.H. Yap
- Seyhan Yazar
- Shea Ping Yip
- Terri L. Young
- Xiangtian Zhou
- Naomi Allen
- Tariq Aslam
- Denize Atan
- Sarah Barman
- Jenny Barrett
- Paul Bishop
- Graeme Black
- Catey Bunce
- Roxana Carare
- Usha Chakravarthy
- Michelle Chan
- Sharon Chua
- Valentina Cipriani
- 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
- Dan Gore
- Jeremy Guggenheim
- Chris Hammond
- Alison Hardcastle
- Simon Harding
- Ruth Hogg
- Pirro Hysi
- Pearse A. Keane
- Peng Tee Khaw
- Anthony Khawaja
- Gerassimos Lascaratos
- Thomas Littlejohns
- Andrew Lotery
- Phil Luthert
- Tom MacGillivray
- Sarah Mackie
- Bernadette McGuinness
- Gareth McKay
- Martin McKibbin
- Danny Mitry
- Tony Moore
- James Morgan
- Zaynah Muthy
- Eoin O'Sullivan
- Chris Owen
- Praveen Patel
- Euan Paterson
- Tunde Peto
- Axel Petzold
- Nikolas Pontikos
- Jugnoo Rahi
- Alicja Rudnicka
- Jay Self
- Panagiotis Sergouniotis
- Sobha Sivaprasad
- David Steel
- Irene Stratton
- Nicholas Strouthidis
- Cathie Sudlow
- Robyn Tapp
- Caroline Thaung
- Dhanes Thomas
- Emanuele Trucco
- Adnan Tufail
- Stephen Vernon
- Ananth Viswanathan
- Veronique Vitart
- Cathy Williams
- Katie Williams
- Jayne Woodside
- Max Yates
- Jennifer Yip
- Yalin Zheng
1 Application
| Application ID | Title |
|---|---|
| 17351 | Genetic risk factors for refractive error |
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