Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Ophthalmology. 2011 Dec;118(12):2389-97. doi: 10.1016/j.ophtha.2011.05.040. Epub 2011 Aug 27.
Genome-wide association studies have revealed new insights into the genetic determinants of open-angle glaucoma (OAG). This study was performed to determine to what extent variants within established genes (MYOC, OPTN, and WDR36) and newly identified common genetic variants (ATOH7, CDKN2B, and SIX1) contribute to the risk of OAG.
Population-based setting, family-based setting, and a case-control study.
The Rotterdam Study I cohort (N = 5312; mean age±standard deviation [SD], 68.0±8.4 years). Findings were replicated in the Genetic Research in Isolated Populations combined with the Erasmus Rucphen Family study (N = 1750; mean age±SD, 48.3±15.2 years), and a cohort from Southampton (N = 702; mean age±SD, 72.5±10.7 years).
After identifying common variants associated with OAG within the established genes, the risk of OAG was analyzed using logistic regression. Discriminative accuracy was assessed by comparing the area under the receiver operator characteristic curve (AUC) for models, including the number of risk alleles, intraocular pressure, age, and gender, with the AUC for the same model but without the risk alleles.
Odds ratios and AUCs of individual and combined risk alleles.
No consistent significant associations for the established genes (MYOC, OPTN, and WDR36) with OAG were found. However, when comparing the load of risk variants between cases and controls, 2 of 3 studies showed a significant increased risk of OAG for participants carrying more risk alleles of the 3 established genes. When combining all 6 genes, participants carrying a high number of risk alleles (highest tertile) had a 2.29-fold to 3.19-fold increase in risk of OAG compared with those carrying only a few risk alleles. The addition of the newly identified genes to IOP, age, and gender resulted in a higher AUC compared with the AUC without the newly identified genes (P = 0.027).
A significant contribution to the risk of OAG was found for the new common variants identified by recent genome-wide association studies, but not for variants within the established genes. Participants carrying a high number of risk alleles had an approximately 3-fold increase in the risk of OAG compared with those with a low number of risk alleles.
FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
全基因组关联研究揭示了开角型青光眼（OAG）遗传决定因素的新见解。本研究旨在确定既定基因（MYOC、OPTN 和 WDR36）内的变体以及新发现的常见遗传变体（ATOH7、CDKN2B 和 SIX1）在多大程度上导致 OAG 风险增加。
基于人群的设置、基于家庭的设置和病例对照研究。
鹿特丹研究 I 队列（N=5312；平均年龄±标准差[SD]，68.0±8.4 岁）。研究结果在遗传研究孤立人群与伊拉斯谟鲁琛家族研究相结合（N=1750；平均年龄±SD，48.3±15.2 岁）和南安普顿队列（N=702；平均年龄±SD，72.5±10.7 岁）中得到了复制。
在确定既定基因中与 OAG 相关的常见变体后，使用逻辑回归分析 OAG 的风险。通过比较包括风险等位基因数、眼内压、年龄和性别在内的模型的接收者操作特征曲线（ROC）下面积（AUC）与不包括风险等位基因的相同模型的 AUC，评估判别准确性。
个体和组合风险等位基因的比值比和 AUC。
没有发现既定基因（MYOC、OPTN 和 WDR36）与 OAG 存在一致的显著关联。然而，当比较病例组和对照组之间的风险变异体负荷时，3 项研究中有 2 项研究显示，携带这 3 个既定基因的更多风险变异体的参与者患 OAG 的风险显著增加。当将所有 6 个基因组合在一起时，与携带少量风险等位基因的参与者相比，携带大量风险等位基因（最高三分位）的参与者患 OAG 的风险增加了 2.29 倍至 3.19 倍。与不包括新鉴定基因的 AUC 相比，将新鉴定基因添加到 IOP、年龄和性别中可获得更高的 AUC（P=0.027）。
最近的全基因组关联研究确定的新常见变体对 OAG 的风险有显著贡献，但既定基因内的变体则不然。与携带少量风险等位基因的参与者相比，携带大量风险等位基因的参与者患 OAG 的风险增加了约 3 倍。
作者没有与本文讨论的材料有任何专有或商业利益。
