TY - JOUR
T1 - Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma
AU - Japan Glaucoma Society Omics Group (JGS-OG)
AU - NEIGHBORHOOD Consortium
AU - Shiga, Yukihiro
AU - Akiyama, Masato
AU - Nishiguchi, Koji M.
AU - Sato, Kota
AU - Shimozawa, Nobuhiro
AU - Takahashi, Atsushi
AU - Momozawa, Yukihide
AU - Hirata, Makoto
AU - Matsuda, Koichi
AU - Yamaji, Taiki
AU - Iwasaki, Motoki
AU - Tsugane, Shoichiro
AU - Oze, Isao
AU - Mikami, Haruo
AU - Naito, Mariko
AU - Wakai, Kenji
AU - Yoshikawa, Munemitsu
AU - Miyake, Masahiro
AU - Yamashiro, Kenji
AU - Kashiwagi, Kenji
AU - Iwata, Takeshi
AU - Mabuchi, Fumihiko
AU - Takamoto, Mitsuko
AU - Ozaki, Mineo
AU - Kawase, Kazuhide
AU - Aihara, Makoto
AU - Araie, Makoto
AU - Yamamoto, Tetsuya
AU - Kiuchi, Yoshiaki
AU - Nakamura, Makoto
AU - Ikeda, Yasuhiro
AU - Sonoda, Koh Hei
AU - Ishibashi, Tatsuro
AU - Nitta, Koji
AU - Iwase, Aiko
AU - Shirato, Shiroaki
AU - Oka, Yoshitaka
AU - Satoh, Mamoru
AU - Sasaki, Makoto
AU - Fuse, Nobuo
AU - Suzuki, Yoichi
AU - Cheng, Ching Yu
AU - Khor, Chiea Chuen
AU - Baskaran, Mani
AU - Perera, Shamira
AU - Aung, Tin
AU - Vithana, Eranga N.
AU - Cooke Bailey, Jessica N.
AU - Kang, Jae H.
AU - Pasquale, Louis R.
N1 - Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press. All rights reserved.
PY - 2018/4/15
Y1 - 2018/4/15
N2 - Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 diseaseassociated 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.
AB - Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 diseaseassociated 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.
UR - http://www.scopus.com/inward/record.url?scp=85045457998&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045457998&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddy053
DO - 10.1093/hmg/ddy053
M3 - Article
C2 - 29452408
AN - SCOPUS:85045457998
SN - 0964-6906
VL - 27
SP - 1486
EP - 1496
JO - Human molecular genetics
JF - Human molecular genetics
IS - 8
ER -