Polygenic Risk Score Predicts Earlier-Onset Adult Systemic Lupus Erythematosus and First-Year Renal Diseases in a Taiwanese Cohort
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
OBJECTIVES: This study aimed to develop a predictive model using polygenic risk score (PRS) to forecast renal outcomes for adult systemic lupus erythematosus (SLE) in a Taiwanese population.
METHODS: Patients with SLE (n=2782) and matched non-SLE controls (n=11 128) were genotyped using Genome-Wide TWB 2.0 single-nucleotide polymorphism (SNP) array. PRS models (C+T, LDpred2, Lassosum, PRSice-2, PRS-continuous shrinkage (CS)) were constructed for predicting SLE susceptibility. Logistic regression was assessed for C+T-based PRS association with renal involvement in patients with SLE.
RESULTS: In the training set, C+T-based SLE-PRS, only incorporating 27 SNPs, outperformed other models with area under the curve (AUC) values of 0.629, surpassing Lassosum (AUC=0.621), PRSice-2 (AUC=0.615), LDpred2 (AUC=0.609) and PRS-CS (AUC=0.602). Additionally, C+T-based SLE-PRS demonstrated consistent predictive capacity in the testing set (AUC=0.620). Individuals in the highest quartile exhibited earlier SLE onset (39.06 vs 44.22 years, p<0.01), higher Systemic Lupus Erythematosus Disease Activity Index scores (3.00 vs 2.37, p=0.04), elevated risks of renal involvement within the first year of SLE diagnosis, including WHO class III-IV lupus nephritis (OR 2.36, 95% CI 1.47 to 3.80, p<0.01), estimated glomerular filtration rate <60 mL/min/1.73m2 (OR 1.49, 95% CI 1.18 to 1.89, p<0.01) and urine protein-to-creatinine ratio >150 mg/day (OR 2.07, 95% CI 1.49 to 2.89, p<0.01), along with increased seropositivity risks, compared with those in the lowest quartile. Furthermore, among patients with SLE with onset before 50 years, the highest PRS quartile was significantly associated with more serious renal diseases within the first year of SLE diagnosis.
CONCLUSIONS: PRS of SLE is associated with earlier onset, renal involvement within the first year of SLE diagnosis and seropositivity in Taiwanese patients. Integrating PRS with clinical decision-making may enhance lupus nephritis screening and early treatment to improve renal outcomes in patients with SLE.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
RMD open - 10(2024), 2 vom: 18. Apr. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Chen, Yen-Ju [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Journal Article |
|---|
| Anmerkungen: |
Date Completed 22.04.2024 Date Revised 22.04.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1136/rmdopen-2023-003293 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM371260892 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM371260892 | ||
| 003 | DE-627 | ||
| 005 | 20240422232526.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240419s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1136/rmdopen-2023-003293 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1383.xml |
| 035 | |a (DE-627)NLM371260892 | ||
| 035 | |a (NLM)38637112 | ||
| 035 | |a (PII)e003293 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Chen, Yen-Ju |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Polygenic Risk Score Predicts Earlier-Onset Adult Systemic Lupus Erythematosus and First-Year Renal Diseases in a Taiwanese Cohort |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 22.04.2024 | ||
| 500 | |a Date Revised 22.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a OBJECTIVES: This study aimed to develop a predictive model using polygenic risk score (PRS) to forecast renal outcomes for adult systemic lupus erythematosus (SLE) in a Taiwanese population | ||
| 520 | |a METHODS: Patients with SLE (n=2782) and matched non-SLE controls (n=11 128) were genotyped using Genome-Wide TWB 2.0 single-nucleotide polymorphism (SNP) array. PRS models (C+T, LDpred2, Lassosum, PRSice-2, PRS-continuous shrinkage (CS)) were constructed for predicting SLE susceptibility. Logistic regression was assessed for C+T-based PRS association with renal involvement in patients with SLE | ||
| 520 | |a RESULTS: In the training set, C+T-based SLE-PRS, only incorporating 27 SNPs, outperformed other models with area under the curve (AUC) values of 0.629, surpassing Lassosum (AUC=0.621), PRSice-2 (AUC=0.615), LDpred2 (AUC=0.609) and PRS-CS (AUC=0.602). Additionally, C+T-based SLE-PRS demonstrated consistent predictive capacity in the testing set (AUC=0.620). Individuals in the highest quartile exhibited earlier SLE onset (39.06 vs 44.22 years, p<0.01), higher Systemic Lupus Erythematosus Disease Activity Index scores (3.00 vs 2.37, p=0.04), elevated risks of renal involvement within the first year of SLE diagnosis, including WHO class III-IV lupus nephritis (OR 2.36, 95% CI 1.47 to 3.80, p<0.01), estimated glomerular filtration rate <60 mL/min/1.73m2 (OR 1.49, 95% CI 1.18 to 1.89, p<0.01) and urine protein-to-creatinine ratio >150 mg/day (OR 2.07, 95% CI 1.49 to 2.89, p<0.01), along with increased seropositivity risks, compared with those in the lowest quartile. Furthermore, among patients with SLE with onset before 50 years, the highest PRS quartile was significantly associated with more serious renal diseases within the first year of SLE diagnosis | ||
| 520 | |a CONCLUSIONS: PRS of SLE is associated with earlier onset, renal involvement within the first year of SLE diagnosis and seropositivity in Taiwanese patients. Integrating PRS with clinical decision-making may enhance lupus nephritis screening and early treatment to improve renal outcomes in patients with SLE | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Lupus Nephritis | |
| 650 | 4 | |a Polymorphism, Genetic | |
| 650 | 4 | |a Systemic Lupus Erythematosus | |
| 700 | 1 | |a Hsiao, Tzu-Hung |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Ying-Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Jeng, Wen-Juei |e verfasserin |4 aut | |
| 700 | 1 | |a Mao, Chien-Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Chia-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Hsieh, Yi-Chung |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Chih-Jen |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Mei-Hung |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, I-Chieh |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Ching-Heng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yi-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Hwai-I |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t RMD open |d 2015 |g 10(2024), 2 vom: 18. Apr. |w (DE-627)NLM254089658 |x 2056-5933 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2024 |g number:2 |g day:18 |g month:04 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1136/rmdopen-2023-003293 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2024 |e 2 |b 18 |c 04 | ||