Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry
Glaucoma is a progressive and irreversible blindness-causing disease. However, the underlying genetic factors and molecular mechanisms remain poorly understood. Previous genome-wide association studies (GWAS) have made tremendous progress on the SNP-based disease association and characterization. Ho...
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2021
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oai:doaj.org-article:8dc8e105b1184138ab966a8335510bc62021-11-25T18:07:45ZGenome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry10.3390/jpm111111692075-4426https://doaj.org/article/8dc8e105b1184138ab966a8335510bc62021-11-01T00:00:00Zhttps://www.mdpi.com/2075-4426/11/11/1169https://doaj.org/toc/2075-4426Glaucoma is a progressive and irreversible blindness-causing disease. However, the underlying genetic factors and molecular mechanisms remain poorly understood. Previous genome-wide association studies (GWAS) have made tremendous progress on the SNP-based disease association and characterization. However, most of them were conducted for Europeans. Since differential genetic characteristics among ethnic groups were evident in glaucoma, it is worthwhile to complete its genetic landscape from the larger cohorts of Asian individuals. Here, we present a GWAS based on the Taiwan Biobank. Among 1013 glaucoma patients and 36,562 controls, we identified a total of 138 independent glaucoma-associated SNPs at the significance level of <i>p</i> < 1 × 10<sup>−5</sup>. After clumping genetically linked SNPs (LD clumping), 134 independent SNPs with <i>p</i> < 10<sup>−4</sup> were recruited to construct a Polygenic Risk Score (PRS). The model achieved an area under the receiver operating characteristic curve (AUC) of 0.8387 (95% CI = [0.8269–0.8506]), and those within the top PRS quantile had a 45.48-fold increased risk of glaucoma compared with those within the lowest quantile. The PRS model was validated with an independent cohort that achieved an AUC of 0.7283, thereby showing the effectiveness of our polygenic risk score in predicting individuals in the Han Chinese population with higher glaucoma risks.Yu-Jer HsiaoHao-Kai ChuangSheng-Chu ChiYung-Yu WangPin-Hsuan ChiangPai-Chi TengTung-Mei KuangAliaksandr A. YarmishynTai-Chi LinDe-Kuang HwangShih-Jen ChenShih-Hwa ChiouMei-Ju ChenAi-Ru HsiehChih-Chien HsuMDPI AGarticleglaucomagenome-wide association studiespolygenic risk scoreAsian populationbiobankretrospective studyMedicineRENJournal of Personalized Medicine, Vol 11, Iss 1169, p 1169 (2021) |
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glaucoma genome-wide association studies polygenic risk score Asian population biobank retrospective study Medicine R |
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glaucoma genome-wide association studies polygenic risk score Asian population biobank retrospective study Medicine R Yu-Jer Hsiao Hao-Kai Chuang Sheng-Chu Chi Yung-Yu Wang Pin-Hsuan Chiang Pai-Chi Teng Tung-Mei Kuang Aliaksandr A. Yarmishyn Tai-Chi Lin De-Kuang Hwang Shih-Jen Chen Shih-Hwa Chiou Mei-Ju Chen Ai-Ru Hsieh Chih-Chien Hsu Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry |
| description |
Glaucoma is a progressive and irreversible blindness-causing disease. However, the underlying genetic factors and molecular mechanisms remain poorly understood. Previous genome-wide association studies (GWAS) have made tremendous progress on the SNP-based disease association and characterization. However, most of them were conducted for Europeans. Since differential genetic characteristics among ethnic groups were evident in glaucoma, it is worthwhile to complete its genetic landscape from the larger cohorts of Asian individuals. Here, we present a GWAS based on the Taiwan Biobank. Among 1013 glaucoma patients and 36,562 controls, we identified a total of 138 independent glaucoma-associated SNPs at the significance level of <i>p</i> < 1 × 10<sup>−5</sup>. After clumping genetically linked SNPs (LD clumping), 134 independent SNPs with <i>p</i> < 10<sup>−4</sup> were recruited to construct a Polygenic Risk Score (PRS). The model achieved an area under the receiver operating characteristic curve (AUC) of 0.8387 (95% CI = [0.8269–0.8506]), and those within the top PRS quantile had a 45.48-fold increased risk of glaucoma compared with those within the lowest quantile. The PRS model was validated with an independent cohort that achieved an AUC of 0.7283, thereby showing the effectiveness of our polygenic risk score in predicting individuals in the Han Chinese population with higher glaucoma risks. |
| format |
article |
| author |
Yu-Jer Hsiao Hao-Kai Chuang Sheng-Chu Chi Yung-Yu Wang Pin-Hsuan Chiang Pai-Chi Teng Tung-Mei Kuang Aliaksandr A. Yarmishyn Tai-Chi Lin De-Kuang Hwang Shih-Jen Chen Shih-Hwa Chiou Mei-Ju Chen Ai-Ru Hsieh Chih-Chien Hsu |
| author_facet |
Yu-Jer Hsiao Hao-Kai Chuang Sheng-Chu Chi Yung-Yu Wang Pin-Hsuan Chiang Pai-Chi Teng Tung-Mei Kuang Aliaksandr A. Yarmishyn Tai-Chi Lin De-Kuang Hwang Shih-Jen Chen Shih-Hwa Chiou Mei-Ju Chen Ai-Ru Hsieh Chih-Chien Hsu |
| author_sort |
Yu-Jer Hsiao |
| title |
Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry |
| title_short |
Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry |
| title_full |
Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry |
| title_fullStr |
Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry |
| title_full_unstemmed |
Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry |
| title_sort |
genome-wide polygenic risk score for predicting high risk glaucoma individuals of han chinese ancestry |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/8dc8e105b1184138ab966a8335510bc6 |
| work_keys_str_mv |
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