To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals. Cross-sectional analysis. Genetic risk scores (GRSs) were constructed based on a genome-wide association study (GWAS) of POAG in Japanese people. A total of 3625 Japanese individuals, including 1191 patients and 2434 controls (Japanese Tohoku), were used for the model selection. We also evaluated the discriminative accuracy of constructed GRSs in a dataset comprising 1034 patients and 1147 controls (the Japan Glaucoma Society Omics Group [JGS-OG] and the Genomic Research Committee of the Japanese Ophthalmological Society [GRC-JOS]) and 1900 participants from a population-based study (Hisayama Study). We evaluated 2 types of GRSs: polygenic risk scores using the pruning and thresholding procedure and a GRS using variants associated with POAG in the GWAS of the International Glaucoma Genetics Consortium (IGGC). We selected the model with the highest areas under the receiver operating characteristic curve (AUC). In the population-based study, we evaluated the correlations between GRS and ocular measurements. Proportion of patients with POAG after stratification according to the GRS. We found that a GRS using 98 variants, which showed genome-wide significance in the IGGC, showed the best discriminative accuracy (AUC, 0.65). In the Japanese Tohoku, the proportion of patients with POAG in the top 10% individuals was significantly higher than that in the lowest 10% (odds ratio [OR], 6.15; 95% confidence interval [CI], 4.35–8.71). In the JGS-OG and GRC-JOS, we confirmed similar impact of POAG GRS (AUC, 0.64; OR [top vs. bottom decile], 5.81; 95% CI, 3.79–9.01). In the population-based study, POAG prevalence was significantly higher in the top 20% individuals of the GRS compared with the bottom 20% (9.2% vs. 5.0%). However, the discriminative accuracy was low (AUC, 0.56). The POAG GRS was correlated positively with intraocular pressure ( = 0.08: = 4.0 × 10) and vertical cup-to-disc ratio ( = 0.11; = 4.0 × 10). The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

中文翻译：

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日本个体原发性开角型青光眼的遗传风险分层


评估遗传风险评估对日本个体原发性开角型青光眼 （POAG） 的影响。横断面分析。遗传风险评分 （GRS） 是根据日本人 POAG 的全基因组关联研究 （GWAS） 构建的。共有 3625 名日本个体，包括 1191 名患者和 2434 名对照 （日本东北），用于模型选择。我们还在由 1034 名患者和 1147 名对照（日本青光眼学会组学组学组 [JGS-OG] 和日本眼科学会基因组研究委员会 [GRC-JOS]）和 1900 名参与者组成的数据集中评估了构建的 GRS 的判别准确性一项基于人群的研究（久山研究）。我们评估了 2 种类型的 GRS：使用修剪和阈值程序的多基因风险评分和使用国际青光眼遗传学联盟 （IGGC） GWAS 中与 POAG 相关的变异的 GRS。我们选择了受试者工作特征曲线 （AUC） 下面积最高的模型。在基于人群的研究中，我们评估了 GRS 与眼部测量之间的相关性。根据 GRS 分层后 POAG 患者的比例。我们发现使用 98 个变体的 GRS 在 IGGC 中显示出全基因组意义，显示出最佳的区分准确性 （AUC，0.65）。在日本东北地区，前 10% 个体的 POAG 患者比例显著高于最低 10% 的个体（比值比 [OR]，6.15;95% 置信区间 [CI]，4.35-8.71）。在 JGS-OG 和 GRC-JOS 中，我们确认了 POAG GRS 的类似影响 （AUC，0.64;或 [顶部 vs. 底部十分位数]，5.81;95% CI，3.79–9.01）。 在基于人群的研究中，GRS 前 20% 个体的 POAG 患病率显著高于后 20% 的个体（9.2% 对 5.0%）。然而，判别准确性较低 （AUC， 0.56）。POAG GRS 与眼压 （ = 0.08： = 4.0 × 10） 和垂直杯盘比 （ = 0.11; = 4.0 × 10） 呈正相关。GRS 显示日本人群中 POAG 的判别准确性适中。然而，一般人群中的风险分层显示出相对较弱的鉴别性能。专有或商业披露可在本文末尾的脚注和披露中找到。