Multiple polygenic risk scores can improve the prediction of systemic lupus erythematosus in Taiwan
Objective To identify new genetic variants associated with SLE in Taiwan and establish polygenic risk score (PRS) models to improve the early diagnostic accuracy of SLE.Methods The study enrolled 2429 patients with SLE and 48 580 controls from China Medical University Hospital in Taiwan. A genome-wi...
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BMJ Publishing Group
2024-05-01
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| Series: | Lupus Science and Medicine |
| Online Access: | https://lupus.bmj.com/content/11/1/e001035.full |
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| author | Fuu-Jen Tsai Chung-Ming Huang Yu-Chia Chen Ting-Yuan Liu Hsing-Fang Lu Chi-Chou Liao |
| author_facet | Fuu-Jen Tsai Chung-Ming Huang Yu-Chia Chen Ting-Yuan Liu Hsing-Fang Lu Chi-Chou Liao |
| author_sort | Fuu-Jen Tsai |
| collection | DOAJ |
| description | Objective To identify new genetic variants associated with SLE in Taiwan and establish polygenic risk score (PRS) models to improve the early diagnostic accuracy of SLE.Methods The study enrolled 2429 patients with SLE and 48 580 controls from China Medical University Hospital in Taiwan. A genome-wide association study (GWAS) and PRS analyses of SLE and other three SLE markers, namely ANA, anti-double-stranded DNA antibody (dsDNA) and anti-Smith antibody (Sm), were conducted.Results Genetic variants associated with SLE were identified through GWAS. Some novel genes, which have been previously reported, such as RCC1L and EGLN3, were revealed to be associated with SLE in Taiwan. Multiple PRS models were established, and optimal cut-off points for each PRS were determined using the Youden Index. Combining the PRSs for SLE, ANA, dsDNA and Sm yielded an area under the curve of 0.64 for the optimal cut-off points. An analysis of human leucocyte antigen (HLA) haplotypes in SLE indicated that individuals with HLA-DQA1*01:01 and HLA-DQB1*05:01 were at a higher risk of being classified into the SLE group.Conclusions The use of PRSs to predict SLE enables the identification of high-risk patients before abnormal laboratory data were obtained or symptoms were manifested. Our findings underscore the potential of using PRSs and GWAS in identifying SLE markers, offering promise for early diagnosis and prediction of SLE. |
| format | Article |
| id | doaj-art-1d24f5e065f249ef95649fc0be2c978d |
| institution | Kabale University |
| issn | 2053-8790 |
| language | English |
| publishDate | 2024-05-01 |
| publisher | BMJ Publishing Group |
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| series | Lupus Science and Medicine |
| spelling | doaj-art-1d24f5e065f249ef95649fc0be2c978d2024-11-10T09:15:08ZengBMJ Publishing GroupLupus Science and Medicine2053-87902024-05-0111110.1136/lupus-2023-001035Multiple polygenic risk scores can improve the prediction of systemic lupus erythematosus in TaiwanFuu-Jen Tsai0Chung-Ming Huang1Yu-Chia Chen2Ting-Yuan Liu3Hsing-Fang Lu4Chi-Chou Liao5China Medical University College of Chinese Medicine, Taichung, TaiwanDivision of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, TaiwanMillion-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, TaiwanMillion-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, TaiwanMillion-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, TaiwanDepartment of Medical Research, China Medical University Hospital, Taichung, TaiwanObjective To identify new genetic variants associated with SLE in Taiwan and establish polygenic risk score (PRS) models to improve the early diagnostic accuracy of SLE.Methods The study enrolled 2429 patients with SLE and 48 580 controls from China Medical University Hospital in Taiwan. A genome-wide association study (GWAS) and PRS analyses of SLE and other three SLE markers, namely ANA, anti-double-stranded DNA antibody (dsDNA) and anti-Smith antibody (Sm), were conducted.Results Genetic variants associated with SLE were identified through GWAS. Some novel genes, which have been previously reported, such as RCC1L and EGLN3, were revealed to be associated with SLE in Taiwan. Multiple PRS models were established, and optimal cut-off points for each PRS were determined using the Youden Index. Combining the PRSs for SLE, ANA, dsDNA and Sm yielded an area under the curve of 0.64 for the optimal cut-off points. An analysis of human leucocyte antigen (HLA) haplotypes in SLE indicated that individuals with HLA-DQA1*01:01 and HLA-DQB1*05:01 were at a higher risk of being classified into the SLE group.Conclusions The use of PRSs to predict SLE enables the identification of high-risk patients before abnormal laboratory data were obtained or symptoms were manifested. Our findings underscore the potential of using PRSs and GWAS in identifying SLE markers, offering promise for early diagnosis and prediction of SLE.https://lupus.bmj.com/content/11/1/e001035.full |
| spellingShingle | Fuu-Jen Tsai Chung-Ming Huang Yu-Chia Chen Ting-Yuan Liu Hsing-Fang Lu Chi-Chou Liao Multiple polygenic risk scores can improve the prediction of systemic lupus erythematosus in Taiwan Lupus Science and Medicine |
| title | Multiple polygenic risk scores can improve the prediction of systemic lupus erythematosus in Taiwan |
| title_full | Multiple polygenic risk scores can improve the prediction of systemic lupus erythematosus in Taiwan |
| title_fullStr | Multiple polygenic risk scores can improve the prediction of systemic lupus erythematosus in Taiwan |
| title_full_unstemmed | Multiple polygenic risk scores can improve the prediction of systemic lupus erythematosus in Taiwan |
| title_short | Multiple polygenic risk scores can improve the prediction of systemic lupus erythematosus in Taiwan |
| title_sort | multiple polygenic risk scores can improve the prediction of systemic lupus erythematosus in taiwan |
| url | https://lupus.bmj.com/content/11/1/e001035.full |
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