QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
University of Tasmania, Hobart, Tasmania, Australia.
Sci Rep. 2018 Feb 15;8(1):3124. doi: 10.1038/s41598-018-20435-9.
Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways - "response to fluid shear stress" and "abnormal retina morphology" - in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.
开角型青光眼（OAG）是全球范围内导致失明的主要原因之一。为了确定 OAG 的新风险基因座，我们对 3071 例 OAG 病例和 6750 例未经筛选的对照进行了全基因组关联研究，并对眼压（IOP）和视盘参数的 GWAS 数据进行了荟萃分析（整体荟萃分析样本量在 32000 至 48000 名参与者之间变化），这些数据与青光眼相关特征有关。我们使用单变量测试在 MYOF 和 CYP26A1、LINC02052 和 CRYGS、LMX1B 和 LMO7 内或附近鉴定并独立验证了四个新的全基因组显著关联，使用基于基因的测试鉴定了另外一个基因座（C9），并使用基于途径的测试鉴定了两个遗传途径-“对流体切应力的反应”和“异常视网膜形态”。有趣的是，一些新的风险基因座与其他遗传相关眼病（包括近视和年龄相关性黄斑变性）的风险有关。据我们所知，这项研究是第一项将 OAG 及其相关特征的遗传数据结合起来识别新的风险变异和遗传途径的综合研究，突出了未来将遗传相关眼病的遗传数据结合起来进行基因发现和图谱绘制的潜力。
