Exploring the Novel Susceptibility Gene Variants for Primary Open-Angle Glaucoma in East Asian Cohorts: The GLAU-GENDISK Study

Yong Woo Kim, Yu Jeong Kim, Hyun Sub Cheong, Yukihiro Shiga, Kazuki Hashimoto, Yong Ju Song, Seok Hwan Kim, Hyuk Jin Choi, Koji M. Nishiguchi, Yosuke Kawai, Masao Nagasaki, Toru Nakazawa, Ki Ho Park, Dong Myung Kim, Jin Wook Jeoung

Research output: Contribution to journalArticle

Abstract

Primary open-angle glaucoma (POAG) can develop even within normal ranges of intraocular pressure, and this type of glaucoma (so-called ‘normal-tension glaucoma [NTG]’) is highly prevalent in East Asia including Korea and Japan. We conducted exome chip analysis to identify low-frequency and rare variants associated with POAG from the primary cohort (309 POAG patients and 5,400 control, all Koreans). For replication, Korean (310 POAG patients and 5,612 controls) and Japanese (565 POAG patients and 1,104 controls) cohorts were further investigated by targeted genotyping. SNP rs116121322 in LRRC27 showed nominally significant association with POAG in the discovery cohort (OR = 29.85, P = 2E–06). This SNP was validated in the Korean replication cohort but only in the NTG subgroups (OR = 9.86, P = 0.007). Japanese replication cohort did not show significant association with POAG (P.00.44). However, the meta-analysis in the entire cohort revealed significant association of rs116121322 with POAG (ORcombined = 10.28, Pcombined = 1.4E–07). The LRRC27 protein expression was confirmed from human trabecular meshwork cells. For gene-based testing, METTL20 showed a significant association in POAG (Pcombined = 0.002) and in the subgroup of NTG (Pcombined = 0.02), whereas ZNF677 were significantly associated with only in the subgroup of high-tension glaucoma (Pcombined = 1.5E–06). Our findings may provide further genetic backgrounds into the pathogenesis of POAG, especially for the patients who have lower baseline intraocular pressures.

Original languageEnglish
Article number221
JournalScientific Reports
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2020

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Genes
Low Tension Glaucoma
Intraocular Pressure
Glaucoma
Single Nucleotide Polymorphism
Primary Open Angle Glaucoma
Exome
Trabecular Meshwork
Far East
Korea
Meta-Analysis
Japan
Reference Values
Proteins

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Kim, Yong Woo ; Kim, Yu Jeong ; Cheong, Hyun Sub ; Shiga, Yukihiro ; Hashimoto, Kazuki ; Song, Yong Ju ; Kim, Seok Hwan ; Choi, Hyuk Jin ; Nishiguchi, Koji M. ; Kawai, Yosuke ; Nagasaki, Masao ; Nakazawa, Toru ; Park, Ki Ho ; Kim, Dong Myung ; Jeoung, Jin Wook. / Exploring the Novel Susceptibility Gene Variants for Primary Open-Angle Glaucoma in East Asian Cohorts : The GLAU-GENDISK Study. In: Scientific Reports. 2020 ; Vol. 10, No. 1.
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abstract = "Primary open-angle glaucoma (POAG) can develop even within normal ranges of intraocular pressure, and this type of glaucoma (so-called ‘normal-tension glaucoma [NTG]’) is highly prevalent in East Asia including Korea and Japan. We conducted exome chip analysis to identify low-frequency and rare variants associated with POAG from the primary cohort (309 POAG patients and 5,400 control, all Koreans). For replication, Korean (310 POAG patients and 5,612 controls) and Japanese (565 POAG patients and 1,104 controls) cohorts were further investigated by targeted genotyping. SNP rs116121322 in LRRC27 showed nominally significant association with POAG in the discovery cohort (OR = 29.85, P = 2E–06). This SNP was validated in the Korean replication cohort but only in the NTG subgroups (OR = 9.86, P = 0.007). Japanese replication cohort did not show significant association with POAG (P.00.44). However, the meta-analysis in the entire cohort revealed significant association of rs116121322 with POAG (ORcombined = 10.28, Pcombined = 1.4E–07). The LRRC27 protein expression was confirmed from human trabecular meshwork cells. For gene-based testing, METTL20 showed a significant association in POAG (Pcombined = 0.002) and in the subgroup of NTG (Pcombined = 0.02), whereas ZNF677 were significantly associated with only in the subgroup of high-tension glaucoma (Pcombined = 1.5E–06). Our findings may provide further genetic backgrounds into the pathogenesis of POAG, especially for the patients who have lower baseline intraocular pressures.",
author = "Kim, {Yong Woo} and Kim, {Yu Jeong} and Cheong, {Hyun Sub} and Yukihiro Shiga and Kazuki Hashimoto and Song, {Yong Ju} and Kim, {Seok Hwan} and Choi, {Hyuk Jin} and Nishiguchi, {Koji M.} and Yosuke Kawai and Masao Nagasaki and Toru Nakazawa and Park, {Ki Ho} and Kim, {Dong Myung} and Jeoung, {Jin Wook}",
year = "2020",
month = "12",
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Kim, YW, Kim, YJ, Cheong, HS, Shiga, Y, Hashimoto, K, Song, YJ, Kim, SH, Choi, HJ, Nishiguchi, KM, Kawai, Y, Nagasaki, M, Nakazawa, T, Park, KH, Kim, DM & Jeoung, JW 2020, 'Exploring the Novel Susceptibility Gene Variants for Primary Open-Angle Glaucoma in East Asian Cohorts: The GLAU-GENDISK Study', Scientific Reports, vol. 10, no. 1, 221. https://doi.org/10.1038/s41598-019-57066-7

Exploring the Novel Susceptibility Gene Variants for Primary Open-Angle Glaucoma in East Asian Cohorts : The GLAU-GENDISK Study. / Kim, Yong Woo; Kim, Yu Jeong; Cheong, Hyun Sub; Shiga, Yukihiro; Hashimoto, Kazuki; Song, Yong Ju; Kim, Seok Hwan; Choi, Hyuk Jin; Nishiguchi, Koji M.; Kawai, Yosuke; Nagasaki, Masao; Nakazawa, Toru; Park, Ki Ho; Kim, Dong Myung; Jeoung, Jin Wook.

In: Scientific Reports, Vol. 10, No. 1, 221, 01.12.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Exploring the Novel Susceptibility Gene Variants for Primary Open-Angle Glaucoma in East Asian Cohorts

T2 - The GLAU-GENDISK Study

AU - Kim, Yong Woo

AU - Kim, Yu Jeong

AU - Cheong, Hyun Sub

AU - Shiga, Yukihiro

AU - Hashimoto, Kazuki

AU - Song, Yong Ju

AU - Kim, Seok Hwan

AU - Choi, Hyuk Jin

AU - Nishiguchi, Koji M.

AU - Kawai, Yosuke

AU - Nagasaki, Masao

AU - Nakazawa, Toru

AU - Park, Ki Ho

AU - Kim, Dong Myung

AU - Jeoung, Jin Wook

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Primary open-angle glaucoma (POAG) can develop even within normal ranges of intraocular pressure, and this type of glaucoma (so-called ‘normal-tension glaucoma [NTG]’) is highly prevalent in East Asia including Korea and Japan. We conducted exome chip analysis to identify low-frequency and rare variants associated with POAG from the primary cohort (309 POAG patients and 5,400 control, all Koreans). For replication, Korean (310 POAG patients and 5,612 controls) and Japanese (565 POAG patients and 1,104 controls) cohorts were further investigated by targeted genotyping. SNP rs116121322 in LRRC27 showed nominally significant association with POAG in the discovery cohort (OR = 29.85, P = 2E–06). This SNP was validated in the Korean replication cohort but only in the NTG subgroups (OR = 9.86, P = 0.007). Japanese replication cohort did not show significant association with POAG (P.00.44). However, the meta-analysis in the entire cohort revealed significant association of rs116121322 with POAG (ORcombined = 10.28, Pcombined = 1.4E–07). The LRRC27 protein expression was confirmed from human trabecular meshwork cells. For gene-based testing, METTL20 showed a significant association in POAG (Pcombined = 0.002) and in the subgroup of NTG (Pcombined = 0.02), whereas ZNF677 were significantly associated with only in the subgroup of high-tension glaucoma (Pcombined = 1.5E–06). Our findings may provide further genetic backgrounds into the pathogenesis of POAG, especially for the patients who have lower baseline intraocular pressures.

AB - Primary open-angle glaucoma (POAG) can develop even within normal ranges of intraocular pressure, and this type of glaucoma (so-called ‘normal-tension glaucoma [NTG]’) is highly prevalent in East Asia including Korea and Japan. We conducted exome chip analysis to identify low-frequency and rare variants associated with POAG from the primary cohort (309 POAG patients and 5,400 control, all Koreans). For replication, Korean (310 POAG patients and 5,612 controls) and Japanese (565 POAG patients and 1,104 controls) cohorts were further investigated by targeted genotyping. SNP rs116121322 in LRRC27 showed nominally significant association with POAG in the discovery cohort (OR = 29.85, P = 2E–06). This SNP was validated in the Korean replication cohort but only in the NTG subgroups (OR = 9.86, P = 0.007). Japanese replication cohort did not show significant association with POAG (P.00.44). However, the meta-analysis in the entire cohort revealed significant association of rs116121322 with POAG (ORcombined = 10.28, Pcombined = 1.4E–07). The LRRC27 protein expression was confirmed from human trabecular meshwork cells. For gene-based testing, METTL20 showed a significant association in POAG (Pcombined = 0.002) and in the subgroup of NTG (Pcombined = 0.02), whereas ZNF677 were significantly associated with only in the subgroup of high-tension glaucoma (Pcombined = 1.5E–06). Our findings may provide further genetic backgrounds into the pathogenesis of POAG, especially for the patients who have lower baseline intraocular pressures.

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