Predictive capabilities of polygenic scores in an East-Asian population-based cohort: the Singapore Chinese health study
Abstract Polygenic scores (PGS) are derived primarily from European population studies. It is unclear how these perform in risk predictions among East-Asians. We generated 2173 PGSs from 519 traits and assessed their associations with 58 baseline phenotypes in the Singapore Chinese Health Study, a p...
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Nature Portfolio
2025-08-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08675-8 |
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| author | Xuling Chang Chih Chuan Shih Jieqi Chen Ai Shan Lee Patrick Tan Ling Wang Jianjun Liu Jingmei Li Jian-Min Yuan Chiea Chuen Khor Woon-Puay Koh Rajkumar Dorajoo |
| author_facet | Xuling Chang Chih Chuan Shih Jieqi Chen Ai Shan Lee Patrick Tan Ling Wang Jianjun Liu Jingmei Li Jian-Min Yuan Chiea Chuen Khor Woon-Puay Koh Rajkumar Dorajoo |
| author_sort | Xuling Chang |
| collection | DOAJ |
| description | Abstract Polygenic scores (PGS) are derived primarily from European population studies. It is unclear how these perform in risk predictions among East-Asians. We generated 2173 PGSs from 519 traits and assessed their associations with 58 baseline phenotypes in the Singapore Chinese Health Study, a prospective cohort of 23,622 Chinese adults residing in Singapore. PGS performances were evaluated through explained variance (r²) and area under the receiver operating characteristic curve (AUC) in linear and logistic regression models, respectively. Traits with higher heritability exhibited stronger PGS associations, while behavioural traits, like sleep duration, showed weaker associations. Height and type 2 diabetes (T2D) exhibited largest SNP-based heritability with the largest increments in explained variance and AUC. We explored the effect of T2D risk factors on the association between the T2D PGS (PGS003444) and incident T2D. PGS associations were significantly mediated and modified by hypertension (P indirect = 1.56 × 10−18, P interaction = 2.10 × 10−3) and BMI (P indirect = 1.25 × 10−36, P interaction = 1.11 × 10−6). Prediction ability of PGS003444 for incident T2D was stronger among non-overweight individuals without hypertension (AUC = 0.774) than in overweight individuals with hypertension (AUC = 0.709). Our study demonstrates the divergent ability of PGSs in predictions of complex traits. For certain traits, such as T2D, PGSs may have the potential for improving risk prediction and personalized healthcare. |
| format | Article |
| id | doaj-art-05ece6ff950f4544b13b790de03a097c |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-05ece6ff950f4544b13b790de03a097c2025-08-20T03:46:21ZengNature PortfolioCommunications Biology2399-36422025-08-01811910.1038/s42003-025-08675-8Predictive capabilities of polygenic scores in an East-Asian population-based cohort: the Singapore Chinese health studyXuling Chang0Chih Chuan Shih1Jieqi Chen2Ai Shan Lee3Patrick Tan4Ling Wang5Jianjun Liu6Jingmei Li7Jian-Min Yuan8Chiea Chuen Khor9Woon-Puay Koh10Rajkumar Dorajoo11Department of Paediatrics, Yong Loo Lin School of Medicine, National University of SingaporeGenome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)UPMC (University of Pittsburgh Medical Center) Hillman Cancer CenterGenome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Paediatrics, Yong Loo Lin School of Medicine, National University of SingaporeAbstract Polygenic scores (PGS) are derived primarily from European population studies. It is unclear how these perform in risk predictions among East-Asians. We generated 2173 PGSs from 519 traits and assessed their associations with 58 baseline phenotypes in the Singapore Chinese Health Study, a prospective cohort of 23,622 Chinese adults residing in Singapore. PGS performances were evaluated through explained variance (r²) and area under the receiver operating characteristic curve (AUC) in linear and logistic regression models, respectively. Traits with higher heritability exhibited stronger PGS associations, while behavioural traits, like sleep duration, showed weaker associations. Height and type 2 diabetes (T2D) exhibited largest SNP-based heritability with the largest increments in explained variance and AUC. We explored the effect of T2D risk factors on the association between the T2D PGS (PGS003444) and incident T2D. PGS associations were significantly mediated and modified by hypertension (P indirect = 1.56 × 10−18, P interaction = 2.10 × 10−3) and BMI (P indirect = 1.25 × 10−36, P interaction = 1.11 × 10−6). Prediction ability of PGS003444 for incident T2D was stronger among non-overweight individuals without hypertension (AUC = 0.774) than in overweight individuals with hypertension (AUC = 0.709). Our study demonstrates the divergent ability of PGSs in predictions of complex traits. For certain traits, such as T2D, PGSs may have the potential for improving risk prediction and personalized healthcare.https://doi.org/10.1038/s42003-025-08675-8 |
| spellingShingle | Xuling Chang Chih Chuan Shih Jieqi Chen Ai Shan Lee Patrick Tan Ling Wang Jianjun Liu Jingmei Li Jian-Min Yuan Chiea Chuen Khor Woon-Puay Koh Rajkumar Dorajoo Predictive capabilities of polygenic scores in an East-Asian population-based cohort: the Singapore Chinese health study Communications Biology |
| title | Predictive capabilities of polygenic scores in an East-Asian population-based cohort: the Singapore Chinese health study |
| title_full | Predictive capabilities of polygenic scores in an East-Asian population-based cohort: the Singapore Chinese health study |
| title_fullStr | Predictive capabilities of polygenic scores in an East-Asian population-based cohort: the Singapore Chinese health study |
| title_full_unstemmed | Predictive capabilities of polygenic scores in an East-Asian population-based cohort: the Singapore Chinese health study |
| title_short | Predictive capabilities of polygenic scores in an East-Asian population-based cohort: the Singapore Chinese health study |
| title_sort | predictive capabilities of polygenic scores in an east asian population based cohort the singapore chinese health study |
| url | https://doi.org/10.1038/s42003-025-08675-8 |
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