TY - JOUR
T1 - Additive effects of genetic variants associated with intraocular pressure in primary open-angle glaucoma
AU - for the 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 - Kawase, Kazuhide
AU - Shiga, Yukihiro
AU - Nishiguchi, Koji M.
AU - Nakazawa, Toru
AU - Ozaki, Mineo
AU - Araie, Makoto
N1 - Funding Information:
>FM has been supported in part by Japan Society for the Promotion of Science (JSPS, URLs http://www.jsps.go.jp) KAKENHI Grant Number 15K10861. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
PY - 2017/8
Y1 - 2017/8
N2 - To investigate the association between the additive effects of genetic variants associated with intraocular pressure (IOP) and IOP, vertical cup-to-disc ratio (VCDR), and high tension glaucoma (HTG) or normal tension glaucoma (NTG) as phenotypic features of primary open-angle glaucoma (POAG), and to evaluate the clinical usefulness of the additive effects of IOP-related genetic variants for predicting IOP elevation, Japanese patients with HTG (n = 255) and NTG (n = 261) and 246 control subjects were genotyped for nine IOP-related genetic variants near CAV2, GAS7, GLCCI1/ICA1, ABCA1, ARHGEF12, FAM125B, FNDC3B, ABO, and PTPRJ/AGBL2. The total number of risk alleles of these genetic variants was calculated for each participant as a genetic risk score (GRS), and the association between the GRS and the maximum IOP, mean VCDR, and phenotype (HTG or NTG) of POAG was evaluated. As the GRS increased, the maximum IOP (P = 0.012) and VCDR (P = 0.010) significantly increased. The GRS (9.1±1.9) in patients with HTG was significantly higher (P = 0.011) than that (8.7±1.8) in control subjects. The patients with GRS12 as a cut-off value had a 2.54 times higher (P = 0.0085) risk on HTG (maximum IOP22mmHg) compared with all patients. The IOP-related GRS approach substantiated that the IOP and VCDR were increased by the additive effects of IOP-related genetic variants in POAG. The high IOP-related GRS in patients with HTG but not NTG shows that there are differences in the genetic background between HTG and NTG and supports the notion that the phenotype (HTG or NTG) in patients with POAG depends on the additive effects of IOP-related genetic variants. The above-mentioned cut-off value of IOP-related GRS may be clinically useful for predicting the risk of IOP elevation.
AB - To investigate the association between the additive effects of genetic variants associated with intraocular pressure (IOP) and IOP, vertical cup-to-disc ratio (VCDR), and high tension glaucoma (HTG) or normal tension glaucoma (NTG) as phenotypic features of primary open-angle glaucoma (POAG), and to evaluate the clinical usefulness of the additive effects of IOP-related genetic variants for predicting IOP elevation, Japanese patients with HTG (n = 255) and NTG (n = 261) and 246 control subjects were genotyped for nine IOP-related genetic variants near CAV2, GAS7, GLCCI1/ICA1, ABCA1, ARHGEF12, FAM125B, FNDC3B, ABO, and PTPRJ/AGBL2. The total number of risk alleles of these genetic variants was calculated for each participant as a genetic risk score (GRS), and the association between the GRS and the maximum IOP, mean VCDR, and phenotype (HTG or NTG) of POAG was evaluated. As the GRS increased, the maximum IOP (P = 0.012) and VCDR (P = 0.010) significantly increased. The GRS (9.1±1.9) in patients with HTG was significantly higher (P = 0.011) than that (8.7±1.8) in control subjects. The patients with GRS12 as a cut-off value had a 2.54 times higher (P = 0.0085) risk on HTG (maximum IOP22mmHg) compared with all patients. The IOP-related GRS approach substantiated that the IOP and VCDR were increased by the additive effects of IOP-related genetic variants in POAG. The high IOP-related GRS in patients with HTG but not NTG shows that there are differences in the genetic background between HTG and NTG and supports the notion that the phenotype (HTG or NTG) in patients with POAG depends on the additive effects of IOP-related genetic variants. The above-mentioned cut-off value of IOP-related GRS may be clinically useful for predicting the risk of IOP elevation.
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U2 - 10.1371/journal.pone.0183709
DO - 10.1371/journal.pone.0183709
M3 - Article
C2 - 28832686
AN - SCOPUS:85028470797
VL - 12
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 8
M1 - e0183709
ER -