Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry
| Autor: | Shih Hwa Chiou, Sheng-Chu Chi, Chih Chien Hsu, De Kuang Hwang, Hao-Kai Chuang, Tung-Mei Kuang, Yung-Yu Wang, Yu-Jer Hsiao, Pin-Hsuan Chiang, Tai-Chi Lin, Aliaksandr A. Yarmishyn, Mei-Ju Chen, Pai-Chi Teng, Ai-Ru Hsieh, Shih Jen Chen |
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| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty business.industry retrospective study Medicine (miscellaneous) Glaucoma Single-nucleotide polymorphism Genome-wide association study Retrospective cohort study Asian population Disease medicine.disease Article biobank glaucoma Internal medicine Cohort genome-wide association studies polygenic risk score Medicine SNP business Genetic association |
| Zdroj: | Journal of Personalized Medicine Volume 11 Issue 11 Journal of Personalized Medicine, Vol 11, Iss 1169, p 1169 (2021) |
| ISSN: | 2075-4426 |
| Popis: | 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 p < 1 × 10−5. After clumping genetically linked SNPs (LD clumping), 134 independent SNPs with p < 10−4 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. |
| Databáze: | OpenAIRE |
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