Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population
Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population
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DOI：
10.1073/pnas.0906397106
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发表时间：
2009-08-04
影响因子：
11.1
通讯作者：
Tashiro, Kei
中科院分区：
文献类型：
--
作者：
Nakano, Masakazu;Ikeda, Yoko;Tashiro, Kei
原发性开角型青光眼(POAG)是青光眼的主要类型。为了发现与POAG相关的遗传标记，我们在全基因组关联研究(阶段1)和随后的研究(阶段2)中检查了总共1,575名日本受试者。两项研究都是在一家机构进行的。在第一阶段关联研究中，我们比较了418名POAG患者和300名对照受试者的SNPs。首先，通过严格的筛选来剔除低质量的数据，并选择331,838个常染色体SNP进行分析。目测评估剔除了聚集不佳的SNP，剩下255个在等位基因频率比较中显示出显著偏差(P<；0.001)。在第二阶段的分析中，我们测试了这255个SNP在409名POAG和448名对照组受试者的DNA样本中的关联性。选择高质量的基因数据，用Mantel-Haenszel检验计算第1、2期的合并P值。这些分析产生了6个SNP，P<；0.0001。在第二阶段，所有6个SNP均显示出显著的相关性(P<；0.05)，证实与POAG有关。虽然我们无法将这些SNPs与注释基因(S)联系起来，但我们已经确定了3个可能与POAG相关的遗传位点。这些发现将为未来的研究提供基础，如荟萃分析，以揭示POAG发病的分子机制。
Primary open-angle glaucoma (POAG) is the major type of glaucoma. To discover genetic markers associated with POAG, we examined a total of 1,575 Japanese subjects in a genome-wide association study (stage 1) and a subsequent study (stage 2). Both studies were carried out at a single institution. In the stage 1 association study, we compared SNPs between 418 POAG patients and 300 control subjects. First, low-quality data were eliminated by a stringent filter, and 331,838 autosomal SNPs were selected for analysis. Poorly clustered SNPs were eliminated by a visual assessment, leaving 255 that showed a significant deviation (P < 0.001) in the allele frequency comparison. In the stage 2 analysis, we tested these 255 SNPs for association in DNA samples from a separate group of 409 POAG and 448 control subjects. High-quality genotype data were selected and used to calculate the combined P values of stages 1 and 2 by the Mantel-Haenszel test. These analyses yielded 6 SNPs with P < 0.0001. All 6 SNPs showed a significant association (P < 0.05) in stage 2, demonstrating a confirmed association with POAG. Although we could not link the SNPs to the annotated gene(s), it turned out that we have identified 3 genetic loci probably associated with POAG. These findings would provide the foundation for future studies to build on, such as for the metaanalysis, to reveal the molecular mechanism of the POAG pathogenesis.