TY - JOUR
T1 - The Potential of Current Polygenic Risk Scores to Predict High Myopia and Myopic Macular Degeneration in Multiethnic Singapore Adults
AU - Kassam, Irfahan
AU - Foo, Li Lian
AU - Lanca, Carla
AU - Xu, Ling Qian
AU - Hoang, Quan V.
AU - Cheng, Ching Yu
AU - Hysi, Pirro
AU - Saw, Seang Mei
N1 - Funding Information:
Supported by the National Medical Research Council, Singapore, Republic of Singapore (grant nos.: NMRC/CIRG/1417/2015, NMRC/CIRG/1488/2018, and NMRC/OFLCG/004a/2018). This analysis was performed using resources provided by the National Supercomputing Centre, Singapore, Singapore, Republic of Singapore (https://www.nscc.sg).
Funding Information:
Supported by the National Medical Research Council , Singapore, Republic of Singapore (grant nos.: NMRC/CIRG/1417/2015, NMRC/CIRG/1488/2018, and NMRC/OFLCG/004a/2018). This analysis was performed using resources provided by the National Supercomputing Centre, Singapore, Singapore, Republic of Singapore ( https://www.nscc.sg ).
Publisher Copyright:
© 2022 American Academy of Ophthalmology
PY - 2022/8
Y1 - 2022/8
N2 - Purpose: To evaluate the transancestry portability of current myopia polygenic risk scores (PRSs) to predict high myopia (HM) and myopic macular degeneration (MMD) in an Asian population. Design: Population-based study. Participants: A total of 5894 adults (2141 Chinese, 1913 Indian, and 1840 Malay) from the Singapore Epidemiology of Eye Diseases study were included in the analysis. The mean ± standard deviation age was 57.05 ± 9.31 years. A total of 361 adults had a diagnosis of HM (spherical equivalent [SE] < –5.00 diopters [D]) from refraction measurements, 240 individuals had a diagnosis of MMD graded by the International Photographic Classification and Grading System for Myopic Maculopathy criteria from fundus photographs, and 3774 individuals were control participants without myopia (SE > –0.5 D). Methods: The PRS, derived from 687 289 HapMap3 single nucleotide polymorphisms (SNPs) from the largest genome-wide association study of myopia in Europeans to date (n = 260 974), was assessed on its ability to predict patients with HM and MMD versus control participants. Main Outcome Measures: The primary outcomes were the area under the receiver operating characteristic curve (AUC) to predict HM and MMD. Results: The PRS had an AUC of 0.73 (95% confidence interval [CI], 0.70–0.75) for HM and 0.66 (95% CI, 0.63–0.70) for MMD versus no myopia. The inclusion of the PRS with other predictors (age, sex, educational attainment [EA], and ancestry; age-by-ancestry, sex-by-ancestry, and EA-by-ancestry interactions; and 20 genotypic principal components) increased the AUC to 0.84 (95% CI, 0.82–0.86) for HM and 0.79 (95% CI, 0.76–0.82) for MMD. Individuals with a PRS in the top 5% showed up to a 4.66 (95% CI, 3.34–6.42) times higher risk of HM developing and up to a 3.43 (95% CI, 2.27–5.05) times higher risk of MMD developing compared with the remaining 95% of individuals. Conclusions: The PRS is a good predictor for HM and facilitates the identification of high-risk children to prevent myopia progression to HM. In addition, the PRS also predicts MMD and helps to identify high-risk adults with myopia who require closer monitoring for myopia-related complications.
AB - Purpose: To evaluate the transancestry portability of current myopia polygenic risk scores (PRSs) to predict high myopia (HM) and myopic macular degeneration (MMD) in an Asian population. Design: Population-based study. Participants: A total of 5894 adults (2141 Chinese, 1913 Indian, and 1840 Malay) from the Singapore Epidemiology of Eye Diseases study were included in the analysis. The mean ± standard deviation age was 57.05 ± 9.31 years. A total of 361 adults had a diagnosis of HM (spherical equivalent [SE] < –5.00 diopters [D]) from refraction measurements, 240 individuals had a diagnosis of MMD graded by the International Photographic Classification and Grading System for Myopic Maculopathy criteria from fundus photographs, and 3774 individuals were control participants without myopia (SE > –0.5 D). Methods: The PRS, derived from 687 289 HapMap3 single nucleotide polymorphisms (SNPs) from the largest genome-wide association study of myopia in Europeans to date (n = 260 974), was assessed on its ability to predict patients with HM and MMD versus control participants. Main Outcome Measures: The primary outcomes were the area under the receiver operating characteristic curve (AUC) to predict HM and MMD. Results: The PRS had an AUC of 0.73 (95% confidence interval [CI], 0.70–0.75) for HM and 0.66 (95% CI, 0.63–0.70) for MMD versus no myopia. The inclusion of the PRS with other predictors (age, sex, educational attainment [EA], and ancestry; age-by-ancestry, sex-by-ancestry, and EA-by-ancestry interactions; and 20 genotypic principal components) increased the AUC to 0.84 (95% CI, 0.82–0.86) for HM and 0.79 (95% CI, 0.76–0.82) for MMD. Individuals with a PRS in the top 5% showed up to a 4.66 (95% CI, 3.34–6.42) times higher risk of HM developing and up to a 3.43 (95% CI, 2.27–5.05) times higher risk of MMD developing compared with the remaining 95% of individuals. Conclusions: The PRS is a good predictor for HM and facilitates the identification of high-risk children to prevent myopia progression to HM. In addition, the PRS also predicts MMD and helps to identify high-risk adults with myopia who require closer monitoring for myopia-related complications.
KW - High myopia
KW - Multiethnic
KW - Myopic macular degeneration
KW - Polygenic risk score
KW - Prediction
UR - http://www.scopus.com/inward/record.url?scp=85130379696&partnerID=8YFLogxK
U2 - 10.1016/j.ophtha.2022.03.022
DO - 10.1016/j.ophtha.2022.03.022
M3 - Article
C2 - 35358591
AN - SCOPUS:85130379696
SN - 0161-6420
VL - 129
SP - 890
EP - 902
JO - Ophthalmology
JF - Ophthalmology
IS - 8
ER -