Genetic Variants Associated With the Onset and Progression of Primary Open-Angle Glaucoma

Fumihiko Mabuchi; Nakako Mabuchi; Yoichi Sakurada; Seigo Yoneyama; Kenji Kashiwagi; Hiroyuki Iijima; Zentaro Yamagata; Mitsuko Takamoto; Makoto Aihara; Takeshi Iwata; Kazuki Hashimoto; Kota Sato; Yukihiro Shiga; Koji M Nishiguchi; Toru Nakazawa; Masato Akiyama; Kazuhide Kawase; Mineo Ozaki; Makoto Araie; Japan Glaucoma Society Omics Group (JGS-OG)

doi:10.1016/j.ajo.2020.03.014

Genetic Variants Associated With the Onset and Progression of Primary Open-Angle Glaucoma

Am J Ophthalmol. 2020 Jul:215:135-140. doi: 10.1016/j.ajo.2020.03.014. Epub 2020 Mar 23.

Authors

Fumihiko Mabuchi¹, Nakako Mabuchi², Yoichi Sakurada², Seigo Yoneyama², Kenji Kashiwagi², Hiroyuki Iijima², Zentaro Yamagata³, Mitsuko Takamoto⁴, Makoto Aihara⁵, Takeshi Iwata⁶, Kazuki Hashimoto⁷, Kota Sato⁸, Yukihiro Shiga⁹, Koji M Nishiguchi¹⁰, Toru Nakazawa¹¹, Masato Akiyama¹², Kazuhide Kawase¹³, Mineo Ozaki¹⁴, Makoto Araie¹⁵; Japan Glaucoma Society Omics Group (JGS-OG)

Collaborators

Japan Glaucoma Society Omics Group (JGS-OG):
Makoto Aihara, Masato Akiyama, Makoto Araie, Kazuki Hashimoto, Takeshi Iwata, Kenji Kashiwagi, Kazuhide Kawase, Fumihiko Mabuchi, Toru Nakazawa, Koji M Nishiguchi, Mineo Ozaki, Kota Sato, Yukihiro Shiga, Mitsuko Takamoto

Affiliations

¹ Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. Electronic address: mabuchif-oph@umin.ac.jp.
² Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
³ Department of Health Sciences, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
⁴ Department of Ophthalmology, Saitama Red Cross Hospital, Saitama, Japan.
⁵ Department of Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
⁶ Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
⁷ Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
⁸ Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan; Collaborative Program for Ophthalmic Drug Discovery, Tohoku University Graduate School of Medicine, Miyagi, Japan.
⁹ Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Miyagi, Japan.
¹⁰ Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan.
¹¹ Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan; Collaborative Program for Ophthalmic Drug Discovery, Tohoku University Graduate School of Medicine, Miyagi, Japan; Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Miyagi, Japan; Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan.
¹² Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹³ Department of Ophthalmolgy, Gifu University Graduate School of Medicine, Gifu, Japan.
¹⁴ Ozaki Eye Hospital, Miyazaki, Japan.
¹⁵ Kanto Central Hospital of the Mutual Aid Association of Public School Teachers, Tokyo, Japan.

PMID: 32217119
DOI: 10.1016/j.ajo.2020.03.014

Abstract

Purpose: We sought to investigate the genetic variants associated with the onset and progression of primary open-angle glaucoma (POAG).

Design: Case-control genetic association study.

Methods: Japanese POAG patients (n = 505) and control subjects (n = 246) were genotyped for 22 genetic variants predisposing to POAG that can be classified into those associated with intraocular pressure (IOP) elevation (IOP-related genetic variants) and optic nerve vulnerability independent of IOP (non-IOP-related genetic variants). The total number of risk alleles of the 17 IOP-related and 5 non-IOP-related genetic variants were calculated as the genetic risk score (GRS), and the associations between the GRS and family history of glaucoma as an indicator of POAG onset and age at the diagnosis of glaucoma as an indicator of POAG progression were evaluated.

Results: There was a significant association (P = .014; odds ratio 1.26 per GRS) between the non-IOP-related GRS, but not IOP-related GRS, and a family history of glaucoma in POAG. As the non-IOP-related GRS increased, the risk of a family history of glaucoma increased. In contrast, a significant association (P = .0014; β = -0.14) was found between the IOP-related GRS, but not non-IOP-related GRS, and age at the diagnosis of glaucoma. As the IOP-related GRS increased, age at the diagnosis of glaucoma decreased.

Conclusion: The results indicate that non-IOP-related (optic nerve vulnerability) rather than IOP-related (IOP elevation) genetic variants may play an important role in the onset of POAG (family history of glaucoma) and that IOP-related rather than non-IOP-related genetic variants may play an important role in its progression (age at the diagnosis of glaucoma).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Case-Control Studies
Disease Progression
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Variation*
Genome-Wide Association Study
Genotyping Techniques
Glaucoma, Open-Angle / diagnosis*
Glaucoma, Open-Angle / genetics*
Humans
Intraocular Pressure / genetics*
Male
Middle Aged
Polymorphism, Single Nucleotide*