| Literature DB >> 29452408 |
Yukihiro Shiga1,2, Masato Akiyama1, Koji M Nishiguchi2,3, Kota Sato2,4, Nobuhiro Shimozawa5, Atsushi Takahashi1,6, Yukihide Momozawa7, Makoto Hirata8, Koichi Matsuda9, Taiki Yamaji10, Motoki Iwasaki10, Shoichiro Tsugane11, Isao Oze12, Haruo Mikami13, Mariko Naito14, Kenji Wakai14, Munemitsu Yoshikawa15, Masahiro Miyake15, Kenji Yamashiro15,16, Kenji Kashiwagi17, Takeshi Iwata18, Fumihiko Mabuchi17, Mitsuko Takamoto19, Mineo Ozaki20,21, Kazuhide Kawase22, Makoto Aihara19, Makoto Araie23, Tetsuya Yamamoto22, Yoshiaki Kiuchi24, Makoto Nakamura25, Yasuhiro Ikeda26, Koh-Hei Sonoda26, Tatsuro Ishibashi26, Koji Nitta27, Aiko Iwase28, Shiroaki Shirato29, Yoshitaka Oka30, Mamoru Satoh31, Makoto Sasaki31, Nobuo Fuse32, Yoichi Suzuki33, Ching-Yu Cheng34,35,36, Chiea Chuen Khor37, Mani Baskaran34,35, Shamira Perera34, Tin Aung34,35,36, Eranga N Vithana34, Jessica N Cooke Bailey38, Jae H Kang39, Louis R Pasquale40, Jonathan L Haines38, Janey L Wiggs40, Kathryn P Burdon41,42, Puya Gharahkhani43, Alex W Hewitt44,45, David A Mackey41,46, Stuart MacGregor43, Jamie E Craig42, R Rand Allingham47, Micheal Hauser48, Adeyinka Ashaye49, Donald L Budenz50, Stephan Akafo51, Susan E I Williams52, Yoichiro Kamatani1,53, Toru Nakazawa2,3,4, Michiaki Kubo7.
Abstract
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 < 5.0×10-8), 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.Entities:
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Year: 2018 PMID： 29452408 PMCID： PMC6251544 DOI： 10.1093/hmg/ddy053
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150