Polygenic Risk Score Predicts Earlier-Onset Adult Systemic Lupus Erythematosus and First-Year Renal Diseases in a Taiwanese Cohort

• Published in: Rheumatic & musculoskeletal diseases open Vol. 10; no. 2; p. e003293
• Main Authors: Chen, Yen-Ju, Hsiao, Tzu-Hung, Lin, Ying-Cheng, Jeng, Wen-Juei, Mao, Chien-Lin, Wei, Chia-Yi, Hsieh, Yi-Chung, Huang, Chih-Jen, Pan, Mei-Hung, Chen, I-Chieh, Lin, Ching-Heng, Chen, Yi-Ming, Yang, Hwai-I
• Format: Journal Article
• Language: English
• Published: England EULAR 18.04.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Original research
• Subjects: Adult; Algorithms; Creatinine; Genetic Risk Score; Genomes; Genotype; Humans; Kidney; Kidney diseases; Lupus; Lupus Erythematosus, Systemic - complications; Lupus Erythematosus, Systemic - diagnosis; Lupus Erythematosus, Systemic - epidemiology; Lupus Nephritis; Lupus Nephritis - diagnosis; Lupus Nephritis - epidemiology; Lupus Nephritis - genetics; Medical records; Methods; Polymorphism, Genetic; Precision medicine; Quality control; Systemic Lupus Erythematosus; Taiwan; Systemic Lupus Erythematosus; Lupus Nephritis; Polymorphism, Genetic
• ISSN: 2056-5933; 2056-5933
• DOI: 10.1136/rmdopen-2023-003293

ObjectivesThis 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.MethodsPatients 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.ResultsIn 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.ConclusionsPRS 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.