Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 x 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, P-meta = 1.60 x 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.
基金:
Biomedical Research Council (BMRC) grant in Singapore [BMRC 10/1/35/19/675]; Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme [NMRC/TCR/008-SERI/2013]; National Medical Research Council, Singapore [NMRC/TCR/002-SERI/2008, (R626/47/2008TCR), CSA R613/34/2008, NMRC 0796/2003, STaR/0003/2008]; National Research Foundation of Singapore; Biomedical Research Council, Singapore [BMRC 09/1/35/19/616, 08/1/35/19/550]; Genome Institute of Singapore [GIS/12-AR2105]; NIH [R01 EY023646, P30-EY005722, HHSN268200782096C, EY015543, EY006827, HL73042, HL073389, EY13315, EY023646, CA87969, CA49449, UM1 CA167552, EY009149]; Collaborative Development of Innovative Seeds of Japan Science and Technology Agency (JST); Ministry of Health, Labor and Welfare of Japan; Santen Pharmaceutical Co. Ltd.; National Natural Science Foundation of China [81030016, 81200723, 81170883, 81430008]; Special Scientific Research Project of Health Professions [201302015]; Health and Medical Research Fund (HMRF), Hong Kong [01122236, 11120801]; General Research Fund from the Research Grants Council, Hong Kong [468810]; National Health and Medical Research Council of Australia [535074, 1023911]; NHMRC [1031362, 1037838, 1048037, 1009844, 1031920]; Alcon Research Institute; BrightFocus Foundation; Ramaciotti Establishment Grant; Australian Research Council (ARC); Queensland Cancer Fund; National Health and Medical Research Council (NHMRC) of Australia [199600, 552429]; National Cancer Institute [5 RO1 CA 001833, R01 CA136725]; Glaucoma Research Chair at College of Medicine, King Saud University, Riyadh, Saudi Arabia; NEI [HG005259-01]; NEI through American Recovery and Reinvestment Act (ARRA) [3R01EY015872-05S1, 3R01EY019126-02S1]; Harvard Glaucoma Center for Excellence; Research to Prevent Blindness; NIH GEI [U01HG04424, U01HG004728]; Singapore Eye Research Institute; The NIH [EY022305, HG004608, EY008208, EY015473, EY012118, EY015682, EY011671, EY09580, EY013178, RR015574, EY015872, EY010886, EY009847, EY014104, EY011008, EY144428, EY144448, EY18660, T32 EY007157, T32 EY21453-2, P30 014104]; National Institute for Health Research [NF-SI-0514-10170] Funding Source: researchfish
第一作者单位:[2]Singapore Eye Res Inst, Singapore, Singapore[4]Genome Inst Singapore, Div Human Genet, Singapore, Singapore
通讯作者:
通讯机构:[1]Academia, Singapore 169856, Singapore[2]Singapore Eye Res Inst, Singapore, Singapore[12]Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore[14]Duke NUS Grad Med Sch, Singapore, Singapore[*1]Academia, 20 Coll Rd,Discovery Tower Level 6, Singapore 169856, Singapore
推荐引用方式(GB/T 7714):
Li Zheng,Allingham R. Rand,Nakano Masakazu,et al.A common variant near TGFBR3 is associated with primary open angle glaucoma[J].HUMAN MOLECULAR GENETICS.2015,24(13):3880-3892.doi:10.1093/hmg/ddv128.
APA:
Li, Zheng,Allingham, R. Rand,Nakano, Masakazu,Jia, Liyun,Chen, Yuhong...&Vithana, Eranga N..(2015).A common variant near TGFBR3 is associated with primary open angle glaucoma.HUMAN MOLECULAR GENETICS,24,(13)
MLA:
Li, Zheng,et al."A common variant near TGFBR3 is associated with primary open angle glaucoma".HUMAN MOLECULAR GENETICS 24..13(2015):3880-3892