Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
Nat Genet. 2011 Jun;43(6):574-8. doi: 10.1038/ng.824. Epub 2011 May 1.
We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma.
我们报告了一项使用 590 名严重视野丧失（病例）和 3956 名对照的发现队列进行的开角型青光眼（OAG）致盲全基因组关联研究。我们在 TMCO1（rs4656461[G]比值比（OR）=1.68，P=6.1×10(-10)) 和 CDKN2B-AS1(rs4977756[A]OR=1.50，P=4.7×10(-9)) 处鉴定到与疾病相关的基因座。我们在另一个具有晚期 OAG 的独立病例队列中（rs4656461 P=0.010；rs4977756 P=0.042）和两个 OAG 严重程度较低的队列中复制了这些关联（rs4656461 发现和复制合并 P=6.00×10(-14)，OR=1.51，95%CI 1.35-1.68；rs4977756 合并 P=1.35×10(-14)，OR=1.39，95%CI 1.28-1.51）。我们在人眼组织中观察到两个基因座的基因在视网膜中的表达。我们还表明，在青光眼大鼠模型中，CDKN2A 和 CDKN2B 在视网膜中上调。
