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Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma


Shiga, Y and Akiyama, M and Nishiguchi, KM and Sato, K and Shimozawa, N and Takahashi, A and Momozawa, Y and Hirata, M and Matsuda, K and Yamaji, T and Iwasaki, M and Tsugane, S and Oze, I and Mikami, H and Naito, M and Wakai, K and Yoshikawa, M and Miyake, M and Yamashiro, K and Kashiwagi, K and Iwata, T and Mabuchi, F and Takamoto, M and Ozaki, M and Kawase, K and Aihara, M and Araie, M and Yamamoto, T and Kiuchi, Y and Nakamura, M and Ikeda, Y and Sonoda, K-H and Ishibashi, T and Nitta, K and Iwase, A and Shirato, S and Oka, Y and Satoh, M and Sasaki, M and Fuse, N and Suzuki, Y and Cheng, C-Y and Khor, CC and Baskaran, M and Perera, S and Aung, T and Vithana, EN and Cooke Bailey, JN and Kang, JH and Pasquale, LR and Haines, JL and Wiggs, JL and Burdon, KP and Gharahkhani, P and Hewitt, AW and Mackey, DA and MacGregor, S and Craig, JE and Allingham, RR and Hauser, M and Ashaye, A and Budenz, DL and Akafo, S and Williams, SEI and Kamatani, Y and Nakazawa, T and Kubo, M, Japan Glaucoma Society Omics Group (JGS-OG), NEIGHBORHOOD Consortium, Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma, Human Molecular Genetics, 27, (8) pp. 1486-1496. ISSN 0964-6906 (2018) [Refereed Article]

Copyright Statement

Copyright 2018 The Authors

DOI: doi:10.1093/hmg/ddy053


Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P < 5.010-8), bringing the total number of POAG-susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a multiethnic population comprising non-Japanese East Asians (1008 cases, 591 controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037 controls). The candidate genes located within the new loci were related to ocular development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B, LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor signaling might be involved in POAG pathogenesis. Genetic correlation analysis revealed the relationships between POAG and systemic diseases, including type 2 diabetes and cardiovascular diseases. These results improve our understanding of the genetic factors that affect the risk of developing POAG and provide new insight into the genetic architecture of POAG in Asians.

Item Details

Item Type:Refereed Article
Keywords:glaucoma, genetic association
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:126985
Year Published:2018
Funding Support:National Health and Medical Research Council (1059954)
Web of Science® Times Cited:68
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-07-06
Last Modified:2019-03-06

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