Importance Primary open-angle glaucoma (POAG) polygenic risk scores (PRSs) continue to be evaluated in primarily European-ancestry populations despite higher prevalence and worse outcomes in African-ancestry populations. Objective To evaluate how established POAG PRSs perform in African-ancestry samples from the Genetics in Glaucoma Patients of African Descent (GIGA), Genetics of Glaucoma in Individuals of African Descent (GGLAD), and Million Veteran Program (MVP) datasets and compare these with European-ancestry samples. Design, Setting, and Participants This was a multicenter, cross-sectional study of POAG cases and controls from Tanzania, South Africa, Nigeria, Ghana, and the US. Included were individuals of African descent from South Africa and Tanzania from the GIGA dataset; individuals of African descent from Ghana, Nigeria, and the US from the GGLAD dataset; and individuals of African or European descent from the US in the MVP dataset. Data were analyzed from January 2022 to July 2023. Exposures Three PRSs derived from large meta-analyses of European and Asian populations, namely Gharahkhani et al (Gharahkhani PRS), Han et al (Han PRS), and Craig et al (Craig PRS). Main Outcomes and Measures Odds ratios (ORs) for POAG risk stratification comparing the highest and lowest quintiles; area under the receiver operating characteristic curve (AUROC), and liability coefficient of determination (R2) for the addition of PRS to a baseline of age, sex, and first 5 principal components. Results A total of 11 673 cases and 66 432 controls were included in this study across 7 ancestral groups. Mean (SD) age of the total participants was 76.9 (8.7) years, with 74 304 males (95.1%). The following were included in each dataset: GIGA (663 cases, 476 controls), GGLAD (1471 cases, 1482 controls), and MVP (9559 cases, 64 474 controls). Increases in ORs were found for the highest POAG risk quintile ranging from an OR of 1.68 (95% CI, 1.17-2.43) in Ghanaians to 7.05 (95% CI, 2.73-19.6) in the South African multiple ancestry group (which derives from at least 5 distinct ancestral groups: Khoisan, Bantus, Europeans, Indians, and Southeast Asians) with the Gharahkhani PRS. The Han PRS showed OR increases for the highest POAG risk quintile ranging from 2.27 (95% CI, 1.49-3.47) in African American individuals in the GGLAD dataset to 7.24 (95% CI, 6.47-8.12) in Europeans. The Craig PRS predicted OR increases in the highest quintile for all groups ranging from 1.51 (95% CI, 1.05-2.18) in Ghanaians to 6.31 (95% CI, 5.67-7.04) in Europeans. However, AUROC and R2 increases above baseline were lower for all African-ancestry compared with European-ancestry groups in the 3 tested PRSs. Conclusions and Relevance In this cross-sectional study, despite some improvements in OR-based risk stratification using the Gharahkhani PRSs, Han PRSs, and Craig PRSs, consistently lower improvements in AUROC and R2 for African-ancestry compared with European-ancestry groups highlight the need for risk prediction models tailored to diverse populations.

中文翻译：

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非洲人后裔人群原发性开角型青光眼多基因风险评分的表现。


重要性 尽管非洲血统人群的患病率较高且结果较差，但继续在主要欧洲血统的人群中评估原发性开角型青光眼 （POAG） 多基因风险评分 （PRS）。目的 评估已建立的 POAG PRS 在非洲血统样本中的表现，这些样本来自非洲血统青光眼患者遗传学 （GIGA）、非洲血统个体青光眼遗传学 （GGLAD） 和百万退伍军人计划 （MVP） 数据集，并将其与欧洲血统样本进行比较。设计、设置和参与者 这是一项针对坦桑尼亚、南非、尼日利亚、加纳和美国的 POAG 病例和控制的多中心横断面研究。包括来自 GIGA 数据集的来自南非和坦桑尼亚的非洲人后裔个体;来自 GGLAD 数据集的来自加纳、尼日利亚和美国的非洲人后裔个体;以及 MVP 数据集中来自美国的非洲或欧洲血统的个人。数据分析时间为 2022 年 1 月至 2023 年 7 月。暴露 来自欧洲和亚洲人群的大型荟萃分析的三个 PRS，即 Gharahkhani 等人 （Gharahkhani PRS）、Han 等人 （Han PRS） 和 Craig 等人 （Craig PRS）。主要结局和措施 POAG 风险分层的比值比 （ORs） 比较最高和最低的五分位数;受试者工作特征曲线下面积 （AUROC） 和将 PRS 添加到年龄、性别和前 5 个主要成分基线的责任决定系数 （R2）。结果 本研究共纳入 7 个祖先群体的 11 673 例病例和 66 432 例对照。总参与者的平均 （SD） 年龄为 76.9 （8.7） 岁，其中男性 74 304 名 （95.1%）。 每个数据集中包括以下内容：GIGA （663 例，476 例对照）、GGLAD （1471 例，1482 例对照）和 MVP （9559 例，64 474 例对照）。发现 POAG 风险最高的五分位数的 OR 增加，从加纳人的 OR 为 1.68（95% CI，1.17-2.43）到南非多血统群体（来自至少 5 个不同的祖先群体：科伊桑人、班图人、欧洲人、印度人和东南亚人）的 OR 为 7.05（95% CI，2.73-19.6）与 Gharahkhani PRS。Han PRS 显示最高 POAG 风险五分位数的 OR 增加范围从 GGLAD 数据集中非裔美国人的 2.27 （95% CI，1.49-3.47） 到欧洲人的 7.24 （95% CI，6.47-8.12）。Craig PRS 预测所有群体最高五分位数的 OR 增加范围从加纳人的 1.51 （95% CI， 1.05-2.18） 到欧洲人的 6.31 （95% CI， 5.67-7.04）。然而，在 3 个测试的 PRS 中，与欧洲血统群体相比，所有非洲血统的 AUROC 和 R2 高于基线的增加都较低。结论和相关性 在这项横断面研究中，尽管使用 Gharahkhani PRS、Han PRS 和 Craig PRS 的基于 OR 的风险分层有一些改进，但与欧洲血统群体相比，非洲血统的 AUROC 和 R2 的改善始终较低，这凸显了为不同人群量身定制的风险预测模型的必要性。