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| PMID |
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| TITLE |
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| 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. |
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| ABSTRACT |
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| BACKGROUND |
NlmCategory: 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 |
NlmCategory: METHODS |
| 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. 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 |
NlmCategory: RESULTS |
| 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. 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. 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 |
NlmCategory: CONCLUSIONS |
| 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. 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. 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). 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 |
NlmCategory: 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. 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. 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). 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. Supported by the Welsh Government and Fight for Sight (24WG201). |
| Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2022/12/08 |
| revised |
2023/03/17 |
| accepted |
2023/03/17 |
| entrez |
2023/04/13 22:00 |
| pubmed |
2023/04/14 06:00 |
| medline |
2023/04/14 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Clark R |
|
Clark |
Rosie |
R |
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School of Optometry & Vision Sciences, Cardiff University, Maindy Road, Cardiff, CF24 4HQ, UK. |
| Lee SS |
|
Lee |
Samantha Sze-Yee |
SS |
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University of Western Australia, Centre for Ophthalmology and Visual Science (incorporating the Lions Eye Institute), Perth, Western Australia, Australia. |
| Du R |
|
Du |
Ran |
R |
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Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 1138510, Japan; Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China. |
| Wang Y |
|
Wang |
Yining |
Y |
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Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 1138510, Japan. |
| Kneepkens SCM |
|
Kneepkens |
Sander C M |
SCM |
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Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands. |
| Charng J |
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Charng |
Jason |
J |
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University of Western Australia, Centre for Ophthalmology and Visual Science (incorporating the Lions Eye Institute), Perth, Western Australia, Australia; Department of Optometry, School of Allied Health, University of Western Australia, Perth, Australia. |
| Huang Y |
|
Huang |
Yu |
Y |
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Department of Ophthalmology, Guangdong Eye Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. |
| Hunter ML |
|
Hunter |
Michael L |
ML |
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Busselton Health Study Centre, Busselton Population Medical Research Institute, Busselton, Western Australia; School of Population and Global Health, University of Western Australia, Perth, Western Australia. |
| Jiang C |
|
Jiang |
Chen |
C |
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Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA. |
| Tideman JWL |
|
Tideman |
J Willem L |
JWL |
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Department of Ophthalmology, Martini Hospital, Groningen, the Netherlands; Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, the Netherlands. |
| Melles RB |
|
Melles |
Ronald B |
RB |
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Department of Ophthalmology Kaiser Permanente Northern California, Redwood City, CA, USA. |
| Klaver CCW |
|
Klaver |
Caroline C W |
CCW |
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Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands; Institute of Molecular and Clinical Ophthalmology, Basel, Switzerland; Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands. |
| Mackey DA |
|
Mackey |
David A |
DA |
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University of Western Australia, Centre for Ophthalmology and Visual Science (incorporating the Lions Eye Institute), Perth, Western Australia, Australia; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, East Melbourne, Victoria, Australia; School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia. |
| Williams C |
|
Williams |
Cathy |
C |
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Centre for Academic Child Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS81NU, UK. |
| Choquet H |
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Choquet |
Hélène |
H |
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Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA. |
| Ohno-Matsui K |
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Ohno-Matsui |
Kyoko |
K |
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Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 1138510, Japan. |
| Guggenheim JA |
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Guggenheim |
Jeremy A |
JA |
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School of Optometry & Vision Sciences, Cardiff University, Maindy Road, Cardiff, CF24 4HQ, UK. Electronic address: guggenheimj1@cardiff.ac.uk. |
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CREAM Consortium |
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UK Biobank Eye and Vision Consortium |
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| INVESTIGATORS |
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| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Bailey-Wilson |
Joan E |
JE |
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| Baird |
Paul N |
PN |
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| Barathi |
Veluchamy A |
VA |
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| Biino |
Ginevra |
G |
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| Burdon |
Kathryn P |
KP |
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| Campbell |
Harry |
H |
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| Chen |
Li Jia |
LJ |
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| Cheng |
Ching-Yu |
CY |
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| Chew |
Emily Y |
EY |
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| Craig |
Jamie E |
JE |
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| Deangelis |
Margaret M |
MM |
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| Delcourt |
Cécile |
C |
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| Ding |
Xiaohu |
X |
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| Fan |
Qiao |
Q |
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| Fossarello |
Maurizio |
M |
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| Foster |
Paul J |
PJ |
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| Gharahkhani |
Puya |
P |
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| Guggenheim |
Jeremy A |
JA |
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| Guo |
Xiaobo |
X |
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| Haarman |
Annechien E G |
AEG |
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| Haller |
Toomas |
T |
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| Hammond |
Christopher J |
CJ |
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| Han |
Xikun |
X |
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| Hayward |
Caroline |
C |
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| He |
Mingguang |
M |
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| Hewitt |
Alex W |
AW |
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| Hoang |
Quan |
Q |
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| Hysi |
Pirro G |
PG |
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| Iglesias |
Adriana I |
AI |
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| Igo |
Robert P |
RP |
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| Iyengar |
Sudha K |
SK |
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| Jonas |
Jost B |
JB |
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| Kähönen |
Mika |
M |
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| Kaprio |
Jaakko |
J |
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| Khawaja |
Anthony P |
AP |
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| Klein |
Barbara E |
BE |
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| Lass |
Jonathan H |
JH |
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| Lee |
Kris |
K |
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| Lehtimäki |
Terho |
T |
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| Lewis |
Deyana |
D |
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| Li |
Qing |
Q |
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| Li |
Shi-Ming |
SM |
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| Lyytikäinen |
Leo-Pekka |
LP |
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| MacGregor |
Stuart |
S |
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| Mackey |
David A |
DA |
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| Martin |
Nicholas G |
NG |
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| Meguro |
Akira |
A |
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| Metspalu |
Andres |
A |
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| Middlebrooks |
Candace |
C |
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| Miyake |
Masahiro |
M |
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| Mizuki |
Nobuhisa |
N |
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| Musolf |
Anthony |
A |
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| Nickels |
Stefan |
S |
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| Oexle |
Konrad |
K |
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| Pang |
Chi Pui |
CP |
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| Pärssinen |
Olavi |
O |
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| Paterson |
Andrew D |
AD |
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| Pfeiffer |
Norbert |
N |
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| Polasek |
Ozren |
O |
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| Rahi |
Jugnoo S |
JS |
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| Raitakari |
Olli |
O |
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| Rudan |
Igor |
I |
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| Sahebjada |
Srujana |
S |
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| Saw |
Seang-Mei |
SM |
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| Simpson |
Claire L |
CL |
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| Stambolian |
Dwight |
D |
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| Tai |
E-Shyong |
ES |
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| Tedja |
Milly S |
MS |
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| Tideman |
J Willem L |
JWL |
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| Tsujikawa |
Akitaka |
A |
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| van Duijn |
Cornelia M |
CM |
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| Verhoeven |
Virginie J M |
VJM |
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| Vitart |
Veronique |
V |
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| Wang |
Ningli |
N |
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| Wang |
Ya Xing |
YX |
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| Wedenoja |
Juho |
J |
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| Wei |
Wen Bin |
WB |
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| Williams |
Cathy |
C |
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| Williams |
Katie M |
KM |
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| Wilson |
James F |
JF |
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| Wojciechowski |
Robert |
R |
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| Yam |
Jason C S |
JCS |
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| Yamashiro |
Kenji |
K |
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| Yap |
Maurice K H |
MKH |
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| Yazar |
Seyhan |
S |
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| Yip |
Shea Ping |
SP |
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| Young |
Terri L |
TL |
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| Zhou |
Xiangtian |
X |
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| Allen |
Naomi |
N |
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| Aslam |
Tariq |
T |
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| Atan |
Denize |
D |
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| Barman |
Sarah |
S |
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| Barrett |
Jenny |
J |
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| Bishop |
Paul |
P |
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| Black |
Graeme |
G |
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| Bunce |
Catey |
C |
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| Carare |
Roxana |
R |
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| Chakravarthy |
Usha |
U |
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| Chan |
Michelle |
M |
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| Chua |
Sharon |
S |
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| Cipriani |
Valentina |
V |
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| Day |
Alexander |
A |
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| Desai |
Parul |
P |
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| Dhillon |
Bal |
B |
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| Dick |
Andrew |
A |
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| Doney |
Alexander |
A |
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| Egan |
Cathy |
C |
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| Ennis |
Sarah |
S |
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| Foster |
Paul |
P |
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| Fruttiger |
Marcus |
M |
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| Gallacher |
John |
J |
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| Garway-Heath |
David |
D |
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| Gibson |
Jane |
J |
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| Gore |
Dan |
D |
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| Guggenheim |
Jeremy |
J |
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| Hammond |
Chris |
C |
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| Hardcastle |
Alison |
A |
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| Harding |
Simon |
S |
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| Hogg |
Ruth |
R |
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| Hysi |
Pirro |
P |
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| Keane |
Pearse A |
PA |
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| Khaw |
Peng Tee |
PT |
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| Khawaja |
Anthony |
A |
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| Lascaratos |
Gerassimos |
G |
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| Littlejohns |
Thomas |
T |
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| Lotery |
Andrew |
A |
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| Luthert |
Phil |
P |
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| MacGillivray |
Tom |
T |
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| Mackie |
Sarah |
S |
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| McGuinness |
Bernadette |
B |
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| McKay |
Gareth |
G |
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| McKibbin |
Martin |
M |
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| Mitry |
Danny |
D |
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| Moore |
Tony |
T |
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| Morgan |
James |
J |
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| Muthy |
Zaynah |
Z |
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| O'Sullivan |
Eoin |
E |
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| Owen |
Chris |
C |
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| Patel |
Praveen |
P |
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| Paterson |
Euan |
E |
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| Peto |
Tunde |
T |
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| Petzold |
Axel |
A |
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| Pontikos |
Nikolas |
N |
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| Rahi |
Jugnoo |
J |
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| Rudnicka |
Alicja |
A |
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| Self |
Jay |
J |
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| Sergouniotis |
Panagiotis |
P |
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| Sivaprasad |
Sobha |
S |
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| Steel |
David |
D |
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| Stratton |
Irene |
I |
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| Strouthidis |
Nicholas |
N |
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| Sudlow |
Cathie |
C |
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| Tapp |
Robyn |
R |
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| Thaung |
Caroline |
C |
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| Thomas |
Dhanes |
D |
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| Trucco |
Emanuele |
E |
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| Tufail |
Adnan |
A |
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| Vernon |
Stephen |
S |
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| Viswanathan |
Ananth |
A |
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| Vitart |
Veronique |
V |
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| Williams |
Cathy |
C |
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| Williams |
Katie |
K |
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| Woodside |
Jayne |
J |
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| Yates |
Max |
M |
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| Yip |
Jennifer |
J |
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| Zheng |
Yalin |
Y |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: EBioMedicine |
| ISOABBREVIATION: EBioMedicine |
| YEAR: 2023 |
| MONTH: Apr |
| DAY: 04 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 2352-3964 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: EBioMedicine |
| COUNTRY: Netherlands |
| ISSNLINKING: 2352-3964 |
| NLMUNIQUEID: 101647039 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| ALSPAC |
| Generation R |
| Myopia |
| Polygenic score |
| UK Biobank |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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