Lupus & antiphospholipid syndrome
Polygenic Risk Score Predicts Earlier-Onset Adult Systemic Lupus Erythematosus and First-Year Renal Diseases in a Taiwanese Cohort
Authors' conclusion
PRS of SLE is associated with earlier onset, renal involvement within the first year of SLE diagnosis and seropositivity in Taiwanese patients.
Study context
- Population
- Adult patients with systemic lupus erythematosus (SLE) and matched non-SLE controls, Taiwanese population, genotyped with TWB 2.0 single-nucleotide polymorphism (SNP) array
- Participants
- 2,782 vs 11,128
- Comparison
- Highest vs lowest SLE-PRS quartile; Polygenic risk score (PRS) models compared for SLE susceptibility prediction
- SLEn = 2,782
- Non-SLE controlsn = 11,128reference
- Outcome
- Prediction of SLE susceptibility by PRS models (AUC); association of C+T-based PRS with renal involvement in SLE
Methodological detailsmatched non-SLE controls, training and testing sets, logistic regression
- Matched non-SLE controls
- Training and testing sets
- Logistic regression
Main finding
As reported in the abstract
SLE susceptibility prediction (AUC), training set
- C+T-based SLE-PRS (27 SNPs) AUC
- 0.629
- Lassosum AUC
- 0.621
- PRSice-2 AUC
- 0.615
- LDpred2 AUC
- 0.609
- PRS-CS AUC
- 0.602
Observational data: associations, not effects.
Further findings
Age at SLE onset, highest vs lowest PRS quartile
P < 0.01
| Outcome | OR (95% CI) | P value | |
|---|---|---|---|
| Renal involvement within first year of SLE diagnosis, highestvs lowest PRS quartileWHO class III-IV LN | 2.36 (1.47–3.80) | P < 0.01 | |
| Renal involvement within first year of SLE diagnosis, highestvs lowest PRS quartileeGFR <60 mL/min/1.73m2 | 1.49 (1.18–1.89) | P < 0.01 | |
| Renal involvement within first year of SLE diagnosis, highestvs lowest PRS quartileUrine protein-to-creatinine ratio >150 mg/day | 2.07 (1.49–2.89) | P < 0.01 | |
| 0.20.5125Odds ratio (log scale) |
| Outcome | Highest quartile | Lowest quartile | P value |
|---|---|---|---|
| SLEDAI scores, highest vs lowest PRS quartile | 3.00 | 2.37 | P = 0.04 |
C+T-based SLE-PRS AUC, testing set
- AUC
- 0.620
Seropositivity, highest vs lowest PRS quartile
- Increased seropositivity risks in highest quartile
Serious renal diseases within first year, SLE onset before 50 years (subgroup) · first year after SLE diagnosis
- Highest PRS quartile significantly associated with more serious renal diseases
Original publication
Polygenic Risk Score Predicts Earlier-Onset Adult Systemic Lupus Erythematosus and First-Year Renal Diseases in a Taiwanese Cohort. RMD Open. Published 18 April 2024. doi:10.
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