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

Japan Glaucoma Society Omics Group (JGS-OG), NEIGHBORHOOD Consortium

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1486-1496
Number of pages11
JournalHuman molecular genetics
Volume27
Issue number8
DOIs
Publication statusPublished - 15-04-2018

Fingerprint

Genome-Wide Association Study
Primary Open Angle Glaucoma
Blindness
Epidermal Growth Factor Receptor
Glaucoma
Type 2 Diabetes Mellitus
Population
Cardiovascular Diseases
Genome
Phenotype

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Japan Glaucoma Society Omics Group (JGS-OG) ; NEIGHBORHOOD Consortium. / Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma. In: Human molecular genetics. 2018 ; Vol. 27, No. 8. pp. 1486-1496.
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abstract = "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.",
author = "{Japan Glaucoma Society Omics Group (JGS-OG)} and {NEIGHBORHOOD Consortium} and Yukihiro Shiga and Masato Akiyama and Nishiguchi, {Koji M.} and Kota Sato and Nobuhiro Shimozawa and Atsushi Takahashi and Yukihide Momozawa and Makoto Hirata and Koichi Matsuda and Taiki Yamaji and Motoki Iwasaki and Shoichiro Tsugane and Isao Oze and Haruo Mikami and Mariko Naito and Kenji Wakai and Munemitsu Yoshikawa and Masahiro Miyake and Kenji Yamashiro and Kenji Kashiwagi and Takeshi Iwata and Fumihiko Mabuchi and Mitsuko Takamoto and Mineo Ozaki and Kazuhide Kawase and Makoto Aihara and Makoto Araie and Tetsuya Yamamoto and Yoshiaki Kiuchi and Makoto Nakamura and Yasuhiro Ikeda and Sonoda, {Koh Hei} and Tatsuro Ishibashi and Koji Nitta and Aiko Iwase and Shiroaki Shirato and Yoshitaka Oka and Mamoru Satoh and Makoto Sasaki and Nobuo Fuse and Yoichi Suzuki and Cheng, {Ching Yu} and Khor, {Chiea Chuen} and Mani Baskaran and Shamira Perera and Tin Aung and Vithana, {Eranga N.} and {Cooke Bailey}, {Jessica N.} and Kang, {Jae H.} and Michiaki Kubo",
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Japan Glaucoma Society Omics Group (JGS-OG) & NEIGHBORHOOD Consortium 2018, 'Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma', Human molecular genetics, vol. 27, no. 8, pp. 1486-1496. https://doi.org/10.1093/hmg/ddy053

Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma. / Japan Glaucoma Society Omics Group (JGS-OG); NEIGHBORHOOD Consortium.

In: Human molecular genetics, Vol. 27, No. 8, 15.04.2018, p. 1486-1496.

Research output: Contribution to journalArticle

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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 - Kubo, Michiaki

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.

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