Polygenic risk scores of rheumatoid arthritis associated with seropositivity and bone erosions in a Taiwanese population
Abstract Polygenic risk scores (PRS) are widely used to estimate disease risks and predict clinical outcomes. However, ethnic differences exist worldwide. We aimed to use PRS for predicting the development of rheumatoid arthritis (RA) in a Taiwanese population and investigate whether PRS of RA may b...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-08254-1 |
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| author | Ting-Shuan Wu Yen-Ju Chen Chia-Ni Hsiung Chien-Lin Mao Chia-Yi Wei I-Chieh Chen Chung-Mao Kao Tzu-Hung Hsiao Wen-Nan Huang Yi-Hsing Chen Yi-Ming Chen |
| author_facet | Ting-Shuan Wu Yen-Ju Chen Chia-Ni Hsiung Chien-Lin Mao Chia-Yi Wei I-Chieh Chen Chung-Mao Kao Tzu-Hung Hsiao Wen-Nan Huang Yi-Hsing Chen Yi-Ming Chen |
| author_sort | Ting-Shuan Wu |
| collection | DOAJ |
| description | Abstract Polygenic risk scores (PRS) are widely used to estimate disease risks and predict clinical outcomes. However, ethnic differences exist worldwide. We aimed to use PRS for predicting the development of rheumatoid arthritis (RA) in a Taiwanese population and investigate whether PRS of RA may be associated with structural damage. PRS was calculated via GWAS data from 2,042 RA patients and 7,950 controls from the Taiwan Precision Medicine Initiative. LDpred2, PLINK, and PRSice-2 models were used to evaluate RA susceptibility via AUC. Clinical factors, including rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), medication, and bone erosion identified by X-ray or ultrasound, were compared across PRS quartiles. PRS derived from 97,396 SNPs via LDpred2 had the highest AUC. Participants in the highest quartile of RA-PRS had the highest proportions of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity (74.8% and 65.0%, respectively), bone erosion (86.4%), and use of bDMARDs or tsDMARDs (42.3%) compared to the other quartiles. PRS remained a significant predictor of bone erosion, particularly in patients under 60 years of age, even after adjusting for RF, ACPA, and treatment. PRS is associated with seropositivity, erosive bone disease, and need for advanced therapy among Taiwanese patients with RA. |
| format | Article |
| id | doaj-art-e56eb975dc3040399866f30dd60ceb11 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-e56eb975dc3040399866f30dd60ceb112025-08-20T03:43:11ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-08254-1Polygenic risk scores of rheumatoid arthritis associated with seropositivity and bone erosions in a Taiwanese populationTing-Shuan Wu0Yen-Ju Chen1Chia-Ni Hsiung2Chien-Lin Mao3Chia-Yi Wei4I-Chieh Chen5Chung-Mao Kao6Tzu-Hung Hsiao7Wen-Nan Huang8Yi-Hsing Chen9Yi-Ming Chen10Department of Biomedical Sciences, Chung Shan Medical UniversityDepartment of Medical Research, Taichung Veterans General HospitalData Science Statistical Cooperation Center, Institute of Statistical Science, Academia SinicaDepartment of Medical Research, Taichung Veterans General HospitalDepartment of Medical Research, Taichung Veterans General HospitalDepartment of Medical Research, Taichung Veterans General HospitalDivision of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General HospitalDepartment of Medical Research, Taichung Veterans General HospitalDivision of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General HospitalDivision of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General HospitalDepartment of Medical Research, Taichung Veterans General HospitalAbstract Polygenic risk scores (PRS) are widely used to estimate disease risks and predict clinical outcomes. However, ethnic differences exist worldwide. We aimed to use PRS for predicting the development of rheumatoid arthritis (RA) in a Taiwanese population and investigate whether PRS of RA may be associated with structural damage. PRS was calculated via GWAS data from 2,042 RA patients and 7,950 controls from the Taiwan Precision Medicine Initiative. LDpred2, PLINK, and PRSice-2 models were used to evaluate RA susceptibility via AUC. Clinical factors, including rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), medication, and bone erosion identified by X-ray or ultrasound, were compared across PRS quartiles. PRS derived from 97,396 SNPs via LDpred2 had the highest AUC. Participants in the highest quartile of RA-PRS had the highest proportions of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity (74.8% and 65.0%, respectively), bone erosion (86.4%), and use of bDMARDs or tsDMARDs (42.3%) compared to the other quartiles. PRS remained a significant predictor of bone erosion, particularly in patients under 60 years of age, even after adjusting for RF, ACPA, and treatment. PRS is associated with seropositivity, erosive bone disease, and need for advanced therapy among Taiwanese patients with RA.https://doi.org/10.1038/s41598-025-08254-1PRSRASeropositivityRheumatoid factorAnti-citrullinated protein antibodyBone erosion |
| spellingShingle | Ting-Shuan Wu Yen-Ju Chen Chia-Ni Hsiung Chien-Lin Mao Chia-Yi Wei I-Chieh Chen Chung-Mao Kao Tzu-Hung Hsiao Wen-Nan Huang Yi-Hsing Chen Yi-Ming Chen Polygenic risk scores of rheumatoid arthritis associated with seropositivity and bone erosions in a Taiwanese population Scientific Reports PRS RA Seropositivity Rheumatoid factor Anti-citrullinated protein antibody Bone erosion |
| title | Polygenic risk scores of rheumatoid arthritis associated with seropositivity and bone erosions in a Taiwanese population |
| title_full | Polygenic risk scores of rheumatoid arthritis associated with seropositivity and bone erosions in a Taiwanese population |
| title_fullStr | Polygenic risk scores of rheumatoid arthritis associated with seropositivity and bone erosions in a Taiwanese population |
| title_full_unstemmed | Polygenic risk scores of rheumatoid arthritis associated with seropositivity and bone erosions in a Taiwanese population |
| title_short | Polygenic risk scores of rheumatoid arthritis associated with seropositivity and bone erosions in a Taiwanese population |
| title_sort | polygenic risk scores of rheumatoid arthritis associated with seropositivity and bone erosions in a taiwanese population |
| topic | PRS RA Seropositivity Rheumatoid factor Anti-citrullinated protein antibody Bone erosion |
| url | https://doi.org/10.1038/s41598-025-08254-1 |
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