Purpose

Genome-wide association studies have identified multiple genetic variants associated with vertical cup-to-disc ratio (VCDR). Genetic risk scores (GRS) examine the aggregate genetic effect of individual variants on a trait by combining these separate genetic variants into a single measure. The purpose of this study was to construct GRS for VCDR and to determine whether the GRS are associated with VCDR and whether the GRS increase the discriminatory ability for primary open-angle glaucoma (POAG) in a Latino population.

Design

Population-based genetic association study.

Participants

A total of 4018 Latino participants recruited from Los Angeles.

Methods

Weighted and unweighted GRS were constructed using 68 previously reported VCDR single nucleotide polymorphisms (SNPs), as well as SNPs from our own genome-wide association data. Linear and logistic regression analyses examined the associations of GRS with VCDR and POAG, respectively. To evaluate the discriminatory ability of the GRS for POAG, we conducted receiver operating characteristic (ROC) analyses.

Main Outcome Measures

The relationship between GRS and VCDR in Latinos.

Results

The GRS were associated significantly with VCDR (P < 0.0001), after adjusting for age, gender, central corneal thickness, intraocular pressure, and education. The weighted GRS explained an additional 2.74% of the variation in VCDR. Adding the weighted GRS derived from previously reported SNPs resulted in a moderate improvement in the discriminatory ability for POAG during ROC analyses, yielding an area under the ROC curve (AUC) of 0.735 (95% CI, 0.701–0.768). When our own SNPs were used, the AUC increased significantly to 0.809 (95% CI, 0.781–0.837; P < 0.0001). We obtained similar results for the unweighted GRS.

Conclusions

To our knowledge, we identified a novel association between GRS and VCDR and its improvement in the discriminatory ability of POAG in a Latino population.

中文翻译：

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遗传风险评分与垂直杯碟比有关，并改善了拉丁美洲人原发性开角型青光眼的预测

目的

全基因组关联研究确定了与垂直杯碟比（VCDR）相关的多种遗传变异。遗传风险评分（GRS）通过将这些单独的遗传变异组合成一个度量来检验单个变异对性状的总体遗传效应。这项研究的目的是构建用于VCDR的GRS，并确定GRS是否与VCDR相关以及GRS是否增加了拉丁美洲人人群原发性开角型青光眼（POAG）的鉴别能力。

设计

基于人群的遗传关联研究。

参加者

从洛杉矶招募了4018名拉丁美洲人。

方法

加权和未加权GRS使用先前报道的68个VCDR单核苷酸多态性（SNP）以及来自我们自己的全基因组关联数据的SNP构建。线性和逻辑回归分析分别检查了GRS与VCDR和POAG的关联。为了评估GRS对POAG的区分能力，我们进行了接收机工作特性（ROC）分析。

主要观察指标

拉美裔人中GRS和VCDR之间的关系。

结果

在调整了年龄，性别，中央角膜厚度，眼压和教育程度后，GRS与VCDR显着相关（P <0.0001）。加权GRS解释了VCDR变异的2.74％。添加从先前报告的SNP得出的加权GRS可以在ROC分析期间适度改善POAG的辨别能力，从而在ROC曲线下的面积（AUC）为0.735（95％CI，0.701-0.768）。当使用我们自己的SNP时，AUC显着增加至0.809（95％CI，0.781–0.837；P <0.0001）。对于未加权的GRS，我们获得了相似的结果。

结论

据我们所知，我们确定了GRS和VCDR之间的新型关联及其在拉丁美洲人口中POAG歧视能力的提高。