Genome-wide analysis identified 17 new loci influencing intraocular pressure in Chinese population
Genome-wide analysis identified 17 new loci influencing intraocular pressure in Chinese population
复制标题
全基因组分析发现了 17 个影响中国人群眼压的新位点
DOI：
10.1007/s11427-018-9430-2
复制
发表时间：
2019-02-01
影响因子：
9.1
通讯作者：
Yang, Zhenglin
中科院分区：
文献类型：
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作者：
Huang, Lulin;Chen, Yuhong;Yang, Zhenglin
眼内压（IOP）是青光眼的主要危险因素。眼内压的遗传决定因素可以为青光眼的遗传结构提供重要的见解，因此，为治疗干预开辟了新的途径。我们对8,552名中国参与者进行了全基因组关联研究和复制分析。在全基因组关联研究中，我们确定了51个超过P <9×10−7显著性的位点，并正式复制了这些位点。一项结合发现和复制的荟萃分析确定了21个超过P <5×10−8的全基因组显著性的基因座，包括4个先前报道的基因座：rs145063132（7p21.2，ETV1/DGKB）、rs548030386（7q31.2，ST7 nearCAV 1/CAV 2）、rs7047871（9p24.2，GLIS3）和rs2472494（9q31.1，ABCA 1/SLC 44 A1）。在17个新发现的基因座中，有5个报告具有眼相关表型：PTCH 2（1p34.1中的rs7525308）、LRIF 1/DRAM 2（1p13.3中的rs 1282146）、COLEC 11（2p25.3中的rs 201143466）、SPTBN 1（2p16.2中的rs 4514918）和CRK（17p13.3中的rs 11078446）。本研究中确定的遗传位点不仅增加了我们对眼内压相关基因的理解，而且为改善未来眼内压疾病的遗传筛查和药物发现提供了重要的遗传标记。
Intraocular pressure (IOP) is a major risk factor for glaucoma. Genetic determinants of intraocular pressure can provide critical insights into the genetic architecture of glaucoma and, as a result, open new avenues for therapeutic intervention. We performed a genome-wide association study and replication analysis of 8,552 Chinese participants. In the genome-wide association study, we identified 51 loci that surpassed the significance ofP<9×10−7, and we formally replicated these loci. A combined discovery and replication meta-analysis identified 21 genome-wide loci that surpassed the genome-wide significance ofP<5×10−8, including 4 previously reported loci: rs145063132 (7p21.2,ETV1/DGKB), rs548030386 (7q31.2,ST7nearCAV1/CAV2), rs7047871 (9p24.2,GLIS3), and rs2472494 (9q31.1, ABCA1/SLC44A1). Of the 17 newly identified loci, five were reported to have ocular related phenotypes:PTCH2(rs7525308 in 1p34.1),LRIF1/DRAM2(rs1282146 in 1p13.3),COLEC11(rs201143466 in 2p25.3),SPTBN1(rs4514918 in 2p16.2), andCRK(rs11078446 in 17p13.3). The genetic loci identified in this study not only increase our understanding of the genes involved in intraocular pressure but also provide important genetic markers to improve future genetic screening and drug discovery for intraocular pressure disorders.