Abstract
Pediatric idiopathic nephrotic syndrome (INS) includes steroid-sensitive (SSNS) and steroid-resistant (SRNS) forms, which differ in treatment response and prognosis. We constructed a polygenic risk score (PRS) using summary statistics from the largest pediatric SSNS GWAS meta-analysis (2,440 cases and 36,023 controls) and evaluated it in an independent Chinese cohort of 2,507 controls, 123 SRNS patients, and 493 SSNS patients. ANOVA showed significant between-group differences (F (2, 3120) = 59.42, P < 2 × 10⁻¹⁶). Post-hoc tests revealed higher PRS in SSNS than controls (P < 0.001), with SRNS intermediate but still elevated compared to controls (P = 0.021) and lower than SSNS (P = 0.001). The elevation of SSNS-derived PRS in SRNS suggests shared polygenic susceptibility between these clinically distinct forms of INS, indicating that overlapping common variants may converge on similar biological pathways and supporting the potential utility of PRS in genetic risk stratification and guiding precision management.
Data availability
Upon reasonable request, the corresponding author will provide the dataset.
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Funding
The study was supported by grants from the Shandong Provincial Natural Science Foundation (ZR2021QH223, ZR2022MH120, ZR2022QH064), Special Funds of Taishan Scholar Project, China (tsqn202211224), the National Natural Science Foundation of China (32270661), Excellent Youth Science Fund Project (Overseas) of Shandong China (2023HWYQ-082), Shandong Postdoctoral Science Foundation (SDCX-ZG-202400042) and Shandong Province Higher Education Institution Youth Innovation and Technology Support Program (2023KJ179).
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Cong Wang and Guotao Yin: Writing—original draft, Data curation, Conceptualization. Yidi Zhou and Yingchao Song: Formal analysis, Data curation. Minle Tian, Xiaoyuan Wang, Jing Wang, Qian Li and Ruixian Zang: Resources, Methdology. Zhenle Yang, Lichun Yu, Suwen Liu, Li Wang, Xiujun Yao and Aihua Zhou: Methodology, Visualization, Software. Shuzhen Sun and Xiao Chang: Conceptualization, Writing—review & editing, Funding acquisition.
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Wang, C., Yin, G., Zhou, Y. et al. Polygenic risk score from steroid-sensitive nephrotic syndrome GWAS indicates overlapping genetic basis with steroid-resistant cases. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38189-0
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DOI: https://doi.org/10.1038/s41598-026-38189-0
