Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, Iowa, United States of America.
PLoS One. 2013;8(3):e58657. doi: 10.1371/journal.pone.0058657. Epub 2013 Mar 11.
Glaucoma and age-related macular degeneration (AMD) are the two leading causes of visual loss in the United States. We utilized a novel study design to perform a genome-wide association for both primary open angle glaucoma (POAG) and AMD. This study design utilized a two-stage process for hypothesis generation and validation, in which each disease cohort was utilized as a control for the other. A total of 400 POAG patients and 400 AMD patients were ascertained and genotyped at 500,000 loci. This study identified a novel association of complement component 7 (C7) to POAG. Additionally, an association of central corneal thickness, a known risk factor for POAG, was found to be associated with ribophorin II (RPN2). Linked monogenic loci for POAG and AMD were also evaluated for evidence of association, none of which were found to be significantly associated. However, several yielded putative associations requiring validation. Our data suggest that POAG is more genetically complex than AMD, with no common risk alleles of large effect.
青光眼和年龄相关性黄斑变性(AMD)是美国导致视力丧失的两个主要原因。我们利用一种新颖的研究设计,对原发性开角型青光眼(POAG)和 AMD 进行全基因组关联分析。该研究设计采用了两阶段的假设生成和验证过程,其中每个疾病队列都被用作另一个疾病队列的对照。共确定了 400 名 POAG 患者和 400 名 AMD 患者,并在 50 万个基因座上进行了基因分型。这项研究发现了补体成分 7(C7)与 POAG 的新关联。此外,还发现了角膜中央厚度(POAG 的已知风险因素)与核糖体磷蛋白 II(RPN2)的关联。还评估了与 POAG 和 AMD 相关的连锁单基因座是否存在关联的证据,但均未发现有显著关联。然而,有几个结果提示存在潜在的关联,需要进一步验证。我们的数据表明,POAG 的遗传复杂性高于 AMD,没有大效应的常见风险等位基因。