Chuang Gwo-Tsann, Hsiung Chia-Ni, Che Tony Pan-Hou, Oh Kook-Hwan, Park Sue K, Moon Sungji, Lee Sangjun, Robinson-Cohen Cassianne, Hung Adriana M, Li Wen-Yi, Chang Yi-Cheng
Division of Nephrology, Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan.
Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan.
J Nephrol. 2025 Sep 4. doi: 10.1007/s40620-025-02380-9.
Kidney function decline is associated with cardiovascular disease and various other morbidities. Previous studies regarding polygenic risk scores of estimated glomerular filtration rate (eGFR) change were generally based on individuals of European ancestry and not validated on populations of East Asian ancestry.
We conducted a genome-wide association study for eGFR slope among 26,755 non-diabetic individuals from the Taiwan Biobank. We developed an eGFR slope polygenic risk score and validated its prediction power on chronic kidney disease (CKD) in another sample with 58,777 non-diabetic individuals.
Eight candidate loci associated with eGFR slope (P-value ranging from 1.56 × 10 to 8.73 × 10) located in the SLC9A9, SLC26A8, DEPTOR, OBP2B, PRMT8, C19orf44 genes and an intergenic locus between MTMR12-ZFR genes were identified and a polygenic risk score for eGFR slope was constructed. The polygenic risk score was validated externally to be significantly associated with CKD in another set of individuals (P-value = 0.0182; odds ratio = 0.753; 95% confidence interval: 0.5936-0.9504).
We constructed a genome-wide polygenic risk score for eGFR decline and externally validated its use in predicting CKD in another Taiwan population. Our eGFR slope polygenic risk score might be useful for clinical CKD risk assessment in future, especially for East Asians.
肾功能下降与心血管疾病及其他多种疾病相关。以往关于估计肾小球滤过率（eGFR）变化的多基因风险评分的研究通常基于欧洲血统个体，未在东亚血统人群中进行验证。
我们对来自台湾生物银行的26755名非糖尿病个体进行了eGFR斜率的全基因组关联研究。我们开发了一个eGFR斜率多基因风险评分，并在另一个包含58777名非糖尿病个体的样本中验证了其对慢性肾脏病（CKD）的预测能力。
鉴定出8个与eGFR斜率相关的候选基因座（P值范围为1.56×10至8.73×10），分别位于SLC9A9、SLC26A8、DEPTOR、OBP2B、PRMT8、C19orf44基因以及MTMR12-ZFR基因之间的一个基因间位点，并构建了eGFR斜率的多基因风险评分。该多基因风险评分在另一组个体中进行外部验证，结果显示与CKD显著相关（P值 = 0.0182；比值比 = 0.753；95%置信区间：0.5936 - 0.9504）。
我们构建了一个用于eGFR下降的全基因组多基因风险评分，并在另一个台湾人群中对其预测CKD的用途进行了外部验证。我们的eGFR斜率多基因风险评分未来可能对临床CKD风险评估有用，尤其是对东亚人群。
