Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma
Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma
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DOI：
10.1038/s41588-018-0176-y
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发表时间：
2018-08-01
期刊：
影响因子：
30.8
通讯作者：
Hewitt, Alex W.
中科院分区：
文献类型：
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作者：
MacGregor, Stuart;Ong, Jue-Sheng;Hewitt, Alex W.
眼内压（IOP）目前是原发性开角型青光眼（POAG）的唯一可改变的风险因素，POAG是全球主要致盲原因之一（1）。IOP和POAG都具有高度遗传性（2）。我们报告了对来自英国生物库的参与者（n = 103，914）和来自国际青光眼遗传联盟的先前发表的数据（n = 29，578）（3，4）的综合分析，确定了101个统计学独立的全基因组显著性IOP SNP，其中85个先前未报道（4-12）。我们在11，018例青光眼病例和126，069例对照中检查了这些SNPs，53个SNPs显示了相关性的证据。基于基因的测试涉及另外22个与IOP相关的独立基因。我们根据IOP位点和影响视神经乳头形态的位点推导出等位基因评分。在1,734名晚期青光眼患者和2,938名对照者中，等位基因得分最高十分位的参与者相对于最低十分位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）。
Intraocular pressure (IOP) is currently the sole modifiable risk factor for primary open-angle glaucoma (POAG), one of the leading causes of blindness worldwide(1). Both IOP and POAG are highly heritable(2). 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)(3,4) that identified 101 statistically independent genome-wide-significant SNPs for IOP, 85 of which have not been previously reported(4-12). 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.