Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
RMD Open. 2024 Apr 18;10(2):e003293. doi: 10.1136/rmdopen-2023-003293.
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.
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.
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/1.73m (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.
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.
本研究旨在建立一个基于多基因风险评分（PRS）的预测模型，以预测台湾人群成年系统性红斑狼疮（SLE）的肾脏结局。
采用全基因组 TWB 2.0 单核苷酸多态性（SNP）芯片对 2782 例 SLE 患者和 11128 例匹配的非 SLE 对照者进行基因分型。构建 PRS 模型（C+T、LDpred2、Lassosum、PRSice-2、PRS-连续收缩（CS））以预测 SLE 易感性。采用 logistic 回归评估基于 C+T 的 PRS 与 SLE 患者肾脏受累的相关性。
在训练集中，仅包含 27 个 SNP 的基于 C+T 的 SLE-PRS 的曲线下面积（AUC）值为 0.629，优于 Lassosum（AUC=0.621）、PRSice-2（AUC=0.615）、LDpred2（AUC=0.609）和 PRS-CS（AUC=0.602）。此外，基于 C+T 的 SLE-PRS 在验证集中也具有一致的预测能力（AUC=0.620）。最高四分位数组的个体 SLE 发病年龄更早（39.06 岁 vs 44.22 岁，p<0.01），SLE 疾病活动指数评分更高（3.00 分 vs 2.37 分，p=0.04），SLE 诊断后第一年发生肾脏受累的风险更高，包括 WHO Ⅲ-Ⅳ狼疮肾炎（OR 2.36，95%CI 1.47-3.80，p<0.01）、肾小球滤过率估计值<60mL/min/1.73m（OR 1.49，95%CI 1.18-1.89，p<0.01）和尿蛋白/肌酐比值>150mg/天（OR 2.07，95%CI 1.49-2.89，p<0.01），且血清学阳性风险更高。此外，在 50 岁前发病的 SLE 患者中，最高 PRS 四分位数组与 SLE 诊断后第一年更严重的肾脏疾病显著相关。
SLE 的 PRS 与台湾患者的发病年龄更早、SLE 诊断后第一年的肾脏受累以及血清学阳性有关。将 PRS 与临床决策相结合可能会增强狼疮肾炎的筛查和早期治疗，以改善 SLE 患者的肾脏结局。
