Polygenic Risk Score Improves Cataract Prediction in East Asian Population
Cataracts, characterized by crystalline lens opacities in human eyes, is the leading cause of blindness globally. Due to its multifactorial complexity, the molecular mechanisms remain poorly understood. Larger cohorts of genome-wide association studies (GWAS) are needed to investigate cataracts’ gen...
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MDPI AG
2022-08-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/8/1920 |
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| author | Chih-Chien Hsu Hao-Kai Chuang Yu-Jer Hsiao Yuan-Chi Teng Pin-Hsuan Chiang Yu-Jun Wang Ting-Yi Lin Ping-Hsing Tsai Chang-Chi Weng Tai-Chi Lin De-Kuang Hwang Ai-Ru Hsieh |
| author_facet | Chih-Chien Hsu Hao-Kai Chuang Yu-Jer Hsiao Yuan-Chi Teng Pin-Hsuan Chiang Yu-Jun Wang Ting-Yi Lin Ping-Hsing Tsai Chang-Chi Weng Tai-Chi Lin De-Kuang Hwang Ai-Ru Hsieh |
| author_sort | Chih-Chien Hsu |
| collection | DOAJ |
| description | Cataracts, characterized by crystalline lens opacities in human eyes, is the leading cause of blindness globally. Due to its multifactorial complexity, the molecular mechanisms remain poorly understood. Larger cohorts of genome-wide association studies (GWAS) are needed to investigate cataracts’ genetic basis. In this study, a GWAS was performed on the largest Han population to date, analyzing a total of 7079 patients and 13,256 controls from the Taiwan Biobank (TWB) 2.0 cohort. Two cataract-associated SNPs with an adjustment of <i>p</i> < 1 × 10<sup>−7</sup> in the older groups and nine SNPs with an adjustment of <i>p</i> < 1 × 10<sup>−6</sup> in the younger group were identified. Except for the reported AGMO in animal models, most variations, including rs74774546 in GJA1 and rs237885 in OXTR, were not identified before this study. Furthermore, a polygenic risk score (PRS) was created for the young and old populations to identify high-risk cataract individuals, with areas under the receiver operating curve (AUROCs) of 0.829 and 0.785, respectively, after covariate adjustments. Younger individuals had 17.45 times the risk while older people had 10.97 times the risk when comparing individuals in the highest and lowest PRS quantiles. Validation analysis on an independent TWB1.0 cohort revealed AUROCs of 0.744 and 0.659. |
| first_indexed | 2024-03-09T10:00:47Z |
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| language | English |
| last_indexed | 2024-03-09T10:00:47Z |
| publishDate | 2022-08-01 |
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| series | Biomedicines |
| spelling | doaj.art-cb06ac1206924dadafd2c3fa8d73bd8a2023-12-01T23:27:53ZengMDPI AGBiomedicines2227-90592022-08-01108192010.3390/biomedicines10081920Polygenic Risk Score Improves Cataract Prediction in East Asian PopulationChih-Chien Hsu0Hao-Kai Chuang1Yu-Jer Hsiao2Yuan-Chi Teng3Pin-Hsuan Chiang4Yu-Jun Wang5Ting-Yi Lin6Ping-Hsing Tsai7Chang-Chi Weng8Tai-Chi Lin9De-Kuang Hwang10Ai-Ru Hsieh11School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, TaiwanDepartment of Medical Research, Taipei Veterans General Hospital, Taipei 112027, TaiwanDepartment of Statistics, Tamkang University, New Taipei 251301, TaiwanDepartment of Statistics, Tamkang University, New Taipei 251301, TaiwanDepartment of Medical Research, Taipei Veterans General Hospital, Taipei 112027, TaiwanDepartment of Medical Research, Taipei Veterans General Hospital, Taipei 112027, TaiwanDepartment of Ophthalmology, Taipei Veterans General Hospital, Taipei 112027, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, TaiwanDepartment of Statistics, Tamkang University, New Taipei 251301, TaiwanCataracts, characterized by crystalline lens opacities in human eyes, is the leading cause of blindness globally. Due to its multifactorial complexity, the molecular mechanisms remain poorly understood. Larger cohorts of genome-wide association studies (GWAS) are needed to investigate cataracts’ genetic basis. In this study, a GWAS was performed on the largest Han population to date, analyzing a total of 7079 patients and 13,256 controls from the Taiwan Biobank (TWB) 2.0 cohort. Two cataract-associated SNPs with an adjustment of <i>p</i> < 1 × 10<sup>−7</sup> in the older groups and nine SNPs with an adjustment of <i>p</i> < 1 × 10<sup>−6</sup> in the younger group were identified. Except for the reported AGMO in animal models, most variations, including rs74774546 in GJA1 and rs237885 in OXTR, were not identified before this study. Furthermore, a polygenic risk score (PRS) was created for the young and old populations to identify high-risk cataract individuals, with areas under the receiver operating curve (AUROCs) of 0.829 and 0.785, respectively, after covariate adjustments. Younger individuals had 17.45 times the risk while older people had 10.97 times the risk when comparing individuals in the highest and lowest PRS quantiles. Validation analysis on an independent TWB1.0 cohort revealed AUROCs of 0.744 and 0.659.https://www.mdpi.com/2227-9059/10/8/1920cataractgenome-wide association studiespolygenic risk scoreAsian populationbiobankretrospective study |
| spellingShingle | Chih-Chien Hsu Hao-Kai Chuang Yu-Jer Hsiao Yuan-Chi Teng Pin-Hsuan Chiang Yu-Jun Wang Ting-Yi Lin Ping-Hsing Tsai Chang-Chi Weng Tai-Chi Lin De-Kuang Hwang Ai-Ru Hsieh Polygenic Risk Score Improves Cataract Prediction in East Asian Population Biomedicines cataract genome-wide association studies polygenic risk score Asian population biobank retrospective study |
| title | Polygenic Risk Score Improves Cataract Prediction in East Asian Population |
| title_full | Polygenic Risk Score Improves Cataract Prediction in East Asian Population |
| title_fullStr | Polygenic Risk Score Improves Cataract Prediction in East Asian Population |
| title_full_unstemmed | Polygenic Risk Score Improves Cataract Prediction in East Asian Population |
| title_short | Polygenic Risk Score Improves Cataract Prediction in East Asian Population |
| title_sort | polygenic risk score improves cataract prediction in east asian population |
| topic | cataract genome-wide association studies polygenic risk score Asian population biobank retrospective study |
| url | https://www.mdpi.com/2227-9059/10/8/1920 |
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