当前多基因风险评分预测多民族新加坡成年人高度近视和近视性黄斑变性的潜力。
The Potential of Current Polygenic Risk Scores to Predict High Myopia and Myopic Macular Degeneration in Multiethnic Singapore Adults.
机构信息
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Republic of Singapore.
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore; Duke-NUS Medical School, Singapore, Republic of Singapore.
出版信息
Ophthalmology. 2022 Aug;129(8):890-902. doi: 10.1016/j.ophtha.2022.03.022. Epub 2022 Mar 28.
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.
目的
评估当前近视多基因风险评分（PRSs）在亚洲人群中预测高度近视（HM）和近视性黄斑变性（MMD）的跨种族适用性。
设计
基于人群的研究。
参与者
纳入新加坡眼病流行病学研究中的 5894 名成年人（2141 名中国人、1913 名印度人和 1840 名马来人）进行分析。平均年龄±标准差为 57.05±9.31 岁。共有 361 名成年人通过折射测量被诊断为 HM（等效球镜[SE]＜-5.00 屈光度[D]），240 名个体通过国际近视性黄斑病变摄影分类和分级系统标准从眼底照片被诊断为 MMD，3774 名成年人作为无近视（SE＞-0.5 D）的对照组参与者。
方法
PRS 源自迄今为止最大的关于欧洲人近视的全基因组关联研究中的 687289 个 HapMap3 单核苷酸多态性（SNP）（n=260974），评估其预测 HM 和 MMD 患者与对照组参与者的能力。
主要观察指标
主要结局是接受者操作特征曲线（ROC）下面积（AUC）来预测 HM 和 MMD。
结果
PRS 对 HM 的 AUC 为 0.73（95%置信区间[CI]，0.70-0.75），对 MMD 的 AUC 为 0.66（95% CI，0.63-0.70），与无近视相比。将 PRS 与其他预测因子（年龄、性别、教育程度[EA]和种族；年龄-种族、性别-种族和 EA-种族相互作用；以及 20 个基因型主成分）相结合，可将 HM 的 AUC 提高至 0.84（95% CI，0.82-0.86），将 MMD 的 AUC 提高至 0.79（95% CI，0.76-0.82）。PRS 处于前 5%的个体患 HM 的风险最高可达 4.66（95% CI，3.34-6.42）倍，患 MMD 的风险最高可达 3.43（95% CI，2.27-5.05）倍，与其余 95%的个体相比。
结论
PRS 是 HM 的良好预测因子，有助于确定高风险儿童，以防止近视进展为 HM。此外，PRS 还可预测 MMD，并有助于识别患有近视的高风险成年人，需要对其进行更密切的近视相关并发症监测。
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