Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population

被引：117

作者：

Arakawa, Satoshi ^{[1
,2
]}

Takahashi, Atsushi ^{[3
]}

Ashikawa, Kyota ^{[1
]}

Hosono, Naoya ^{[1
]}

Aoi, Tomomi ^{[1
]}

Yasuda, Miho ^{[2
]}

Oshima, Yuji ^{[2
]}

Yoshida, Shigeo ^{[2
]}

Enaida, Hiroshi ^{[2
]}

Tsuchihashi, Takashi ^{[4
]}

Mori, Keisuke ^{[4
]}

Honda, Shigeru ^{[5
]}

Negi, Akira ^{[5
]}

Arakawa, Akira ^{[6
]}

Kadonosono, Kazuaki ^{[6
]}

Kiyohara, Yutaka ^{[7
]}

Kamatani, Naoyuki ^{[3
]}

Nakamura, Yusuke ^{[8
]}

Ishibashi, Tatsuro ^{[2
]}

Kubo, Michiaki ^{[1
]}

机构：

[1] RIKEN Yokohama Inst, Ctr Genom Med, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[2] Kyushu Univ, Dept Ophthalmol, Grad Sch Med Sci, Fukuoka 812, Japan

[3] RIKEN Yokohama Inst, Ctr Genom Med, Lab Stat Anal, Yokohama, Kanagawa, Japan

[4] Saitama Med Univ, Dept Ophthalmol, Saitama, Japan

[5] Kobe Univ, Grad Sch Med, Div Ophthalmol, Dept Surg, Kobe, Hyogo 657, Japan

[6] Yokohama City Univ, Dept Ophthalmol, Med Ctr, Yokohama, Kanagawa 232, Japan

[7] Kyushu Univ, Dept Environm Med, Grad Sch Med Sci, Fukuoka 812, Japan

[8] Univ Tokyo, Inst Med Sci, Mol Med Lab, Ctr Human Genome, Tokyo, Japan

来源：

NATURE GENETICS | 2011年 / 43卷 / 10期

关键词：

RETINAL ANGIOMATOUS PROLIFERATION; POLYPOIDAL CHOROIDAL VASCULOPATHY; TOMOGRAPHIC FEATURES; GENETIC-VARIANTS; FACTOR-B; POLYMORPHISM; APOPTOSIS; RISK; PATHWAY; LINKAGE;

D O I：

10.1038/ng.938

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Age-related macular degeneration (AMD), the leading cause of irreversible blindness in the world, is a complex disease caused by multiple environmental and genetic risk factors. To identify genetic factors that modify the risk of exudative AMD in the Japanese population, we conducted a genome-wide association study and a replication study using a total of 1,536 individuals with exudative AMD and 18,894 controls. In addition to CFH (rs800292, P = 4.23 x 10(-15)) and ARMS2 (rs3750847, P = 8.67 x 10(-29)) loci, we identified two new susceptibility loci for exudative AMD: TNFRSF10A-LOC389641 on chromosome 8p21 (rs13278062, combined P = 1.03 x 10(-12), odds ratio = 0.73) and REST-C4orf14-POLR2B-IGFBP7 on chromosome 4q12 (rs1713985, combined P = 2.34 x 10(-8), odds ratio = 1.30). Fine mapping revealed that rs13278062, which is known to alter TNFRSF10A transcriptional activity, had the most significant association in 8p21 region. Our results provide new insights into the pathophysiology of exudative AMD.

引用

页码：1001 / U114

页数：5

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