QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Nat Genet. 2018 Aug;50(8):1067-1071. doi: 10.1038/s41588-018-0176-y. Epub 2018 Jul 27.
Intraocular pressure (IOP) is currently the sole modifiable risk factor for primary open-angle glaucoma (POAG), one of the leading causes of blindness worldwide. Both IOP and POAG are highly heritable. We report a combined analysis of participants from the UK Biobank (n = 103,914) and previously published data from the International Glaucoma Genetic Consortium (n = 29,578) that identified 101 statistically independent genome-wide-significant SNPs for IOP, 85 of which have not been previously reported. We examined these SNPs in 11,018 glaucoma cases and 126,069 controls, and 53 SNPs showed evidence of association. Gene-based tests implicated an additional 22 independent genes associated with IOP. We derived an allele score based on the IOP loci and loci influencing optic nerve head morphology. In 1,734 people with advanced glaucoma and 2,938 controls, participants in the top decile of the allele score were at increased risk (odds ratio (OR) = 5.6; 95% confidence interval (CI): 4.1-7.6) of glaucoma relative to the bottom decile.
眼压 (IOP) 是原发性开角型青光眼 (POAG) 的唯一可改变的危险因素，POAG 是全球致盲的主要原因之一。IOP 和 POAG 的遗传性都很高。我们报告了来自英国生物银行（n = 103914）的参与者的联合分析和先前发表的国际青光眼遗传联合会的数据（n = 29578），这些数据确定了 101 个与 IOP 相关的全基因组显著 SNP，其中 85 个以前没有报道过。我们在 11018 例青光眼病例和 126069 例对照中检查了这些 SNP，其中 53 个 SNP 显示出与疾病相关的证据。基于基因的测试表明，还有另外 22 个与 IOP 相关的独立基因。我们基于IOP 基因座和影响视神经头形态的基因座，推导了一个等位基因分数。在 1734 名晚期青光眼患者和 2938 名对照者中，等位基因分数最高的十分之一的参与者患青光眼的风险增加（比值比 (OR) = 5.6；95%置信区间 (CI)：4.1-7.6）相对较低的十分之一。
