TY - JOUR
T1 - 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
AU - CREAM Consortium
AU - UK Biobank Eye and Vision Consortium
AU - Clark, Rosie
AU - Lee, Samantha Sze Yee
AU - Du, Ran
AU - Wang, Yining
AU - Kneepkens, Sander C.M.
AU - Charng, Jason
AU - Huang, Yu
AU - Hunter, Michael L.
AU - Jiang, Chen
AU - Tideman, J. Willem L.
AU - Melles, Ronald B.
AU - Klaver, Caroline C.W.
AU - Mackey, David A.
AU - Williams, Cathy
AU - Choquet, Hélène
AU - Ohno-Matsui, Kyoko
AU - Guggenheim, Jeremy
AU - Bailey-Wilson, Joan E.
AU - Baird, Paul N.
AU - Barathi, Veluchamy A.
AU - Biino, Ginevra
AU - Burdon, Kathryn P.
AU - Campbell, Harry
AU - Chen, Li Jia
AU - Cheng, Ching Yu
AU - Chew, Emily Y.
AU - Craig, Jamie E.
AU - Deangelis, Margaret M.
AU - Delcourt, Cécile
AU - Ding, Xiaohu
AU - Fan, Qiao
AU - Fossarello, Maurizio
AU - Foster, Paul J.
AU - Gharahkhani, Puya
AU - Guo, Xiaobo
AU - Haarman, Annechien E.G.
AU - Haller, Toomas
AU - Hammond, Christopher J.
AU - Han, Xikun
AU - Hayward, Caroline
AU - He, Mingguang
AU - Hewitt, Alex W.
AU - Hoang, Quan
AU - Hysi, Pirro
AU - Iglesias, Adriana I.
AU - Igo, Robert P.
AU - Iyengar, Sudha K.
AU - Jonas, Jost B.
AU - Kähönen, Mika
AU - Kaprio, Jaakko
AU - Khawaja, Anthony
AU - Klein, Barbara E.
AU - Lass, Jonathan H.
AU - Lee, Kris
AU - Lehtimäki, Terho
AU - Lewis, Deyana
AU - Li, Qing
AU - Li, Shi Ming
AU - Lyytikäinen, Leo Pekka
AU - MacGregor, Stuart
AU - Martin, Nicholas G.
AU - Meguro, Akira
AU - Metspalu, Andres
AU - Middlebrooks, Candace
AU - Miyake, Masahiro
AU - Mizuki, Nobuhisa
AU - Musolf, Anthony
AU - Nickels, Stefan
AU - Oexle, Konrad
AU - Pang, Chi Pui
AU - Pärssinen, Olavi
AU - Paterson, Andrew D.
AU - Pfeiffer, Norbert
AU - Polasek, Ozren
AU - Rahi, Jugnoo
AU - Raitakari, Olli
AU - Rudan, Igor
AU - Sahebjada, Srujana
AU - Saw, Seang Mei
AU - Simpson, Claire L.
AU - Stambolian, Dwight
AU - Tai, E. Shyong
AU - Tedja, Milly S.
AU - Tideman, J. Willem L.
AU - Tsujikawa, Akitaka
AU - van Duijn, Cornelia M.
AU - Verhoeven, Virginie J.M.
AU - Vitart, Veronique
AU - Wang, Ningli
AU - Wang, Ya Xing
AU - Wedenoja, Juho
AU - Wei, Wen Bin
AU - Williams, Katie M.
AU - Wilson, James F.
AU - Wojciechowski, Robert
AU - Yam, Jason C.S.
AU - Yamashiro, Kenji
AU - Yap, Maurice K.H.
AU - Yazar, Seyhan
AU - Yip, Shea Ping
AU - Young, Terri L.
AU - Zhou, Xiangtian
AU - Allen, Naomi
AU - Aslam, Tariq
AU - Atan, Denize
AU - Barman, Sarah
AU - Barrett, Jenny
AU - Bishop, Paul
AU - Black, Graeme
AU - Bunce, Catey
AU - Carare, Roxana
AU - Chakravarthy, Usha
AU - Chan, Michelle
AU - Chua, Sharon
AU - Cipriani, Valentina
AU - Day, Alexander
AU - Desai, Parul
AU - Dhillon, Bal
AU - Dick, Andrew
AU - Doney, Alexander
AU - Egan, Cathy
AU - Ennis, Sarah
AU - Foster, Paul
AU - Fruttiger, Marcus
AU - Gallacher, John
AU - Garway-Heath, David
AU - Gibson, Jane
AU - Gore, Dan
AU - Guggenheim, Jeremy
AU - Hammond, Chris
AU - Hardcastle, Alison
AU - Harding, Simon
AU - Hogg, Ruth
AU - Hysi, Pirro
AU - Keane, Pearse A.
AU - Khaw, Peng Tee
AU - Khawaja, Anthony
AU - Lascaratos, Gerassimos
AU - Littlejohns, Thomas
AU - Lotery, Andrew
AU - Luthert, Phil
AU - MacGillivray, Tom
AU - Mackie, Sarah
AU - McGuinness, Bernadette
AU - McKay, Gareth
AU - McKibbin, Martin
AU - Mitry, Danny
AU - Moore, Tony
AU - Morgan, James
AU - Muthy, Zaynah
AU - O'Sullivan, Eoin
AU - Owen, Chris
AU - Patel, Praveen
AU - Paterson, Euan
AU - Peto, Tunde
AU - Petzold, Axel
AU - Pontikos, Nikolas
AU - Rahi, Jugnoo
AU - Rudnicka, Alicja
AU - Self, Jay
AU - Sergouniotis, Panagiotis
AU - Sivaprasad, Sobha
AU - Steel, David
AU - Stratton, Irene
AU - Strouthidis, Nicholas
AU - Sudlow, Cathie
AU - Tapp, Robyn
AU - Thaung, Caroline
AU - Thomas, Dhanes
AU - Trucco, Emanuele
AU - Tufail, Adnan
AU - Vernon, Stephen
AU - Viswanathan, Ananth
AU - Williams, Katie
AU - Woodside, Jayne
AU - Yates, Max
AU - Yip, Jennifer
AU - Zheng, Yalin
PY - 2023/5
Y1 - 2023/5
N2 - 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. 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. 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). 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. Funding: Supported by the Welsh Government and Fight for Sight ( 24WG201).
AB - 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. 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. 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). 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. Funding: Supported by the Welsh Government and Fight for Sight ( 24WG201).
KW - ALSPAC
KW - Generation R
KW - Myopia
KW - Polygenic score
KW - UK Biobank
UR - http://www.scopus.com/inward/record.url?scp=85153851999&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2023.104551
DO - 10.1016/j.ebiom.2023.104551
M3 - Article
C2 - 37055258
AN - SCOPUS:85153851999
SN - 2352-3964
VL - 91
JO - EBioMedicine
JF - EBioMedicine
M1 - 104551
ER -