TY - JOUR
T1 - Genetic Variants Associated With the Onset and Progression of Primary Open-Angle Glaucoma
AU - Japan Glaucoma Society Omics Group (JGS-OG)
AU - Mabuchi, Fumihiko
AU - Mabuchi, Nakako
AU - Sakurada, Yoichi
AU - Yoneyama, Seigo
AU - Kashiwagi, Kenji
AU - Iijima, Hiroyuki
AU - Yamagata, Zentaro
AU - Takamoto, Mitsuko
AU - Aihara, Makoto
AU - Iwata, Takeshi
AU - Hashimoto, Kazuki
AU - Sato, Kota
AU - Shiga, Yukihiro
AU - Nishiguchi, Koji M.
AU - Nakazawa, Toru
AU - Akiyama, Masato
AU - Kawase, Kazuhide
AU - Ozaki, Mineo
AU - Araie, Makoto
N1 - Funding Information:
All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. Funding/Support: Supported in part by Japan Society for the Promotion of Science (JSPS) Japan, KAKENHI Grants 15K10861 and 18K09400. The sponsor or funding organization had no role in the design or conduct of this research. Financial Disclosures: Dr Aihara has received grants from Alcon Japan, Alcon Pharma Japan, AMO Japan, CREWT Medical Systems, Glaukos, Kowa, Nitten, Novartis Pharma Japan, Ono, Otsuka, Pfizer Japan, Santen Japan, Senju, TOMEY, and Wakamoto, has been a consultant for Alcon Japan, Alcon Pharma Japan, CREWT Medical Systems, Glaukos, HOYA, InnFocus, IRIDEX, Kowa, Nitten, Ono, Otsuka, Pfizer Japan, Santen Japan, Senju, and Wakamoto, has received lecture fees from Alcon Japan, Alcon Pharma Japan, Canon, Carl Zeiss Meditec, CREWT Medical Systems, Glaukos, HOYA, IRIDEX, Kowa, Nitten, Novartis Pharma Japan, Otsuka, Pfizer Japan, Santen Japan, Senju, and TOMEY. Dr Araie has been a consultant for Aerie, Santen Japan, and Topcon, received honoraria from Alcon Japan, Heidelberg Engineering, Kowa, Otsuka, Pfizer Japan, and Senju, is a board member for Kowa, Pfizer Japan and Senju, and has a patent from Topcon. Drs F. Mabuchi, N. Mabuchi, Sakurada, Yoneyama, Kashiwagi, Iijima, Yamagata, Takamoto, Iwata, Hashimoto, Sato, Shiga, Nishiguchi, Nakazawa, Akiyama, Kawase, and Ozaki have no financial conflicts of interest to disclose. Conceptualization (F.M.); Methodology (F.M. K.Kas.); Formal analysis (F.M. Z.Y.); Investigation (F.M. N.M. Y.S. S.Y.); Resources (F.M. Y.S. M.T.); Writing - original draft, (F.M.); Writing - review and editing (N.M. Y.S. S.Y. K.Kas. H.I. Z.Y. M.T. M.Ai. T.I. K.H. K.S. Y.S. K.M.N. T.N. M.Ak. K.Kaw. M.O. M.Ar.); Visualization (F.M.); Project administration (F.M. K.H. K.S. Y.S. K.M.N. M.Ak. K.Kaw. M.O.); Funding acquisition (F.M.); Supervision (K.Kas. H.I. M.Ai. T.I. T.N. M.Ar.). All authors attest that they meet the current ICMJE criteria for authorship.
Funding Information:
All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. Funding/Support: Supported in part by Japan Society for the Promotion of Science (JSPS) Japan, KAKENHI Grants 15K10861 and 18K09400. The sponsor or funding organization had no role in the design or conduct of this research. Financial Disclosures: Dr Aihara has received grants from Alcon Japan, Alcon Pharma Japan, AMO Japan, CREWT Medical Systems, Glaukos, Kowa, Nitten, Novartis Pharma Japan, Ono, Otsuka, Pfizer Japan, Santen Japan, Senju, TOMEY, and Wakamoto, has been a consultant for Alcon Japan, Alcon Pharma Japan, CREWT Medical Systems, Glaukos, HOYA, InnFocus, IRIDEX, Kowa, Nitten, Ono, Otsuka, Pfizer Japan, Santen Japan, Senju, and Wakamoto, has received lecture fees from Alcon Japan, Alcon Pharma Japan, Canon, Carl Zeiss Meditec, CREWT Medical Systems, Glaukos, HOYA, IRIDEX, Kowa, Nitten, Novartis Pharma Japan, Otsuka, Pfizer Japan, Santen Japan, Senju, and TOMEY. Dr Araie has been a consultant for Aerie, Santen Japan, and Topcon, received honoraria from Alcon Japan, Heidelberg Engineering, Kowa, Otsuka, Pfizer Japan, and Senju, is a board member for Kowa, Pfizer Japan and Senju, and has a patent from Topcon. Drs F. Mabuchi, N. Mabuchi, Sakurada, Yoneyama, Kashiwagi, Iijima, Yamagata, Takamoto, Iwata, Hashimoto, Sato, Shiga, Nishiguchi, Nakazawa, Akiyama, Kawase, and Ozaki have no financial conflicts of interest to disclose. Conceptualization (F.M.); Methodology (F.M., K.Kas.); Formal analysis (F.M., Z.Y.); Investigation (F.M., N.M., Y.S., S.Y.); Resources (F.M., Y.S., M.T.); Writing - original draft, (F.M.); Writing - review and editing (N.M., Y.S., S.Y., K.Kas., H.I., Z.Y., M.T., M.Ai., T.I., K.H., K.S., Y.S., K.M.N., T.N., M.Ak., K.Kaw., M.O., M.Ar.); Visualization (F.M.); Project administration (F.M., K.H., K.S., Y.S., K.M.N., M.Ak., K.Kaw., M.O.); Funding acquisition (F.M.); Supervision (K.Kas., H.I., M.Ai., T.I., T.N., M.Ar.). All authors attest that they meet the current ICMJE criteria for authorship.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/7
Y1 - 2020/7
N2 - 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).
AB - 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).
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U2 - 10.1016/j.ajo.2020.03.014
DO - 10.1016/j.ajo.2020.03.014
M3 - Article
C2 - 32217119
AN - SCOPUS:85084746322
SN - 0002-9394
VL - 215
SP - 135
EP - 140
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
ER -