Genetic Risk Stratification of Primary Open-Angle Glaucoma in Japanese Individuals

Masato Akiyama,Masato Akiyama,Gen Tamiya,Kohta Fujiwara,Yukihiro Shiga,Yukihiro Shiga,Yukihiro Shiga,Yu Yokoyama,Kazuki Hashimoto,Masataka Sato,Kota Sato,Kota Sato,Akira Narita,Sawako Hashimoto,Emi Ueda,Yoshihiko Furuta,Jun Hata,Masahiro Miyake,Hanako O Ikeda,Kenji Suda,Shogo Numa,Yuki Mori,Kazuya Morino,Yusuke Murakami,Sakurako Shimokawa,Shun Nakamura,Nobuyo Yawata,Kimihiko Fujisawa,Satoshi Yamana,Kenichiro Mori,Yasuhiro Ikeda,Kazunori Miyata,Keisuke Mori,Ken Ogino,Yoshito Koyanagi,Yoichiro Kamatani,Koichi Matsuda,Yuji Yamanashi,Yoichi Furukawa,Takayuki Morisaki,Yukinori Okada,Yoshinori Murakami,Kaori Muto,Akiko Nagai,Yusuke Nakamura,Wataru Obara,Ken Yamaji,Kazuhisa Takahashi,Satoshi Asai,Yasuo Takahashi,Shinichi Higashiue,Shuzo Kobayashi,Hiroki Yamaguchi,Yasunobu Nagata,Satoshi Wakita,Chikako Nito,Yu-Ki Iwasaki,Shigeo Murayama,Kozo Yoshimori,Yoshio Miki,Daisuke Obata,Masahiko Higashiyama,Akihide Masumoto,Yoshinobu Koga,Yukihiro Koretsune,Toshiharu Ninomiya,Koh-Hei Sonoda,Toru Nakazawa,Toru Nakazawa,Toru Nakazawa,Toru Nakazawa,Makoto Aihara,Rei Sakata,Kenji Kashiwagi,Fumihiko Mabuchi,Kazuhide Kawase,Takeshi Iwata,Motokazu Tsujikawa,Koji M Nishiguchi

doi:10.1016/j.ophtha.2024.05.026

Abstract

To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals. Cross-sectional analysis. Genetic risk scores (GRSs) were constructed based on a genome-wide association study (GWAS) of POAG in Japanese people. A total of 3625 Japanese individuals, including 1191 patients and 2434 controls (Japanese Tohoku), were used for the model selection. We also evaluated the discriminative accuracy of constructed GRSs in a dataset comprising 1034 patients and 1147 controls (the Japan Glaucoma Society Omics Group [JGS-OG] and the Genomic Research Committee of the Japanese Ophthalmological Society [GRC-JOS]) and 1900 participants from a population-based study (Hisayama Study). We evaluated 2 types of GRSs: polygenic risk scores using the pruning and thresholding procedure and a GRS using variants associated with POAG in the GWAS of the International Glaucoma Genetics Consortium (IGGC). We selected the model with the highest areas under the receiver operating characteristic curve (AUC). In the population-based study, we evaluated the correlations between GRS and ocular measurements. Proportion of patients with POAG after stratification according to the GRS. We found that a GRS using 98 variants, which showed genome-wide significance in the IGGC, showed the best discriminative accuracy (AUC, 0.65). In the Japanese Tohoku, the proportion of patients with POAG in the top 10% individuals was significantly higher than that in the lowest 10% (odds ratio [OR], 6.15; 95% confidence interval [CI], 4.35-8.71). In the JGS-OG and GRC-JOS, we confirmed similar impact of POAG GRS (AUC, 0.64; OR [top vs. bottom decile], 5.81; 95% CI, 3.79-9.01). In the population-based study, POAG prevalence was significantly higher in the top 20% individuals of the GRS compared with the bottom 20% (9.2% vs. 5.0%). However, the discriminative accuracy was low (AUC, 0.56). The POAG GRS was correlated positively with intraocular pressure (r= 0.08: P= 4.0× 10-4) and vertical cup-to-disc ratio (r= 0.11; P= 4.0× 10-6). The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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