Common genetic variants associated with open-angle glaucoma
Common genetic variants associated with open-angle glaucoma
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DOI：
10.1093/hmg/ddr120
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发表时间：
2011-06-15
影响因子：
3.5
通讯作者：
van Duijn, Cornelia M.
中科院分区：
文献类型：
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作者：
Ramdas, Wishal D.;van Koolwijk, Leonieke M. E.;van Duijn, Cornelia M.
开角型青光眼（青光眼）是一种以视盘病理为特征的主要眼部疾病。最近的全基因组关联研究确定了与临床相关的视盘参数，如视盘面积和垂直杯盘比（VCDR）相关的新位点。我们研究了这些位点在多大程度上参与青光眼。研究的基因座包括视盘区的ATOH 7、CDC 7/TGFBR 3和SALL 1，以及VCDR的CDKN 2B、SIX 1、SCYL 1/LTBP 3、CHEK 2、ATOH 7和DCLK 1。我们使用六项独立研究的数据进行了荟萃分析，包括：鹿特丹研究（n = 5736），隔离人群的遗传学研究结合伊拉斯谟鲁克芬家系研究（n = 1750）、阿姆斯特丹青光眼研究（n = 296）以及来自埃尔兰根和图宾根的队列（n = 1363）、南安普顿（n = 702）和deCODE（n = 36151），总共产生3161个青光眼病例和42837个对照。在这八个位点中，我们发现了重要的证据（P = 1.41 x 10（-8）），CDKN 2B与青光眼的相关性[风险等位基因纯合子的比值比（OR）：0.76; 95%置信区间（CI）：0.70-0.84]，ATOH 7的作用（OR：1.28; 95%CI：1.12-1.47）和SIX1（OR：1.20; 95%CI：1.10-1.31）。此外，CDC 7/TGFBR 3和SALL 1与青光眼存在临界显著相关性（均P = 0.04）。总之，我们发现了三种常见变异（CDKN 2B，ATOH 7和SIX 1）与青光眼显著相关的一致证据。这些发现可能揭示了导致青光眼的病理生理蛋白通路，并指出了参与视神经生长和发育的通路。
Open-angle glaucoma (glaucoma) is a major eye disorder characterized by optic disc pathology. Recent genome-wide association studies identified new loci associated with clinically relevant optic disc parameters, such as the optic disc area and vertical cup-disc ratio (VCDR). We examined to what extent these loci are involved in glaucoma. The loci studied include ATOH7, CDC7/TGFBR3 and SALL1 for optic disc area, and CDKN2B, SIX1, SCYL1/LTBP3, CHEK2, ATOH7 and DCLK1 for VCDR. We performed a meta-analysis using data from six independent studies including: the Rotterdam Study (n = 5736), Genetic Research in Isolated Populations combined with Erasmus Rucphen Family study (n = 1750), Amsterdam Glaucoma Study (n = 296) and cohorts from Erlangen and Tubingen (n = 1363), Southampton (n = 702) and deCODE (n = 36 151) resulting in a total of 3161 glaucoma cases and 42 837 controls. Of the eight loci, we found significant evidence (P = 1.41 x 10(-8)) for the association of CDKN2B with glaucoma [odds ratio (OR) for those homozygous for the risk allele: 0.76; 95% confidence interval (CI): 0.70-0.84], for the role of ATOH7 (OR: 1.28; 95% CI: 1.12-1.47) and for SIX1 (OR: 1.20; 95% CI: 1.10-1.31) when adjusting for the number of tested loci. Furthermore, there was a borderline significant association of CDC7/TGFBR3 and SALL1 (both P = 0.04) with glaucoma. In conclusion, we found consistent evidence for three common variants (CDKN2B, ATOH7 and SIX1) significantly associated with glaucoma. These findings may shed new light on the pathophysiological protein pathways leading to glaucoma, and point to pathways involved in the growth and development of the optic nerve.