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Abstract: TH-OR29

A Multi-Population Polygenic Risk Score for Pediatric Steroid Sensitive Nephrotic Syndrome Is Correlated With Disease Age at Onset

Session Information

Category: Pediatric Nephrology

  • 1800 Pediatric Nephrology


  • Nagano, China, Boston Children's Hospital, Boston, United States
  • Barry, Alexandra, Boston Children's Hospital, Boston, Massachusetts, United States
  • Mcnulty, Michelle, Boston Children's Hospital, Boston, Massachusetts, United States
  • Sampson, Matt G., Boston Children's Hospital, Boston, Massachusetts, United States

Group or Team Name


Genome wide association studies (GWAS) have implicated thousands of single nucleotide polymorphisms (SNPs) in common complex diseases and traits. These SNPs can be combined to generate polygenic risk scores (PRS) that can be used for subsequent predictions and clinical association studies. There are no know PRSs of nephrotic syndrome (NS). In this study, we created a multi-population PRS of pediatric steroid sensitive nephrotic syndrome (SSNS) from the largest GWAS of this disease ever conducted and examined its relationship with clinical phenotypes in two independent cohorts.


The PRS for SSNS was constructed using PRS-CSx, which improves PRS prediction by integrating GWAS from multiple populations. We used GWAS summary statistics derived from European (361 cases and 4309 controls) and Asian (1364 cases and 7954 controls) datasets to generate population-specific PRSs. We used an independent European pediatric SSNS cohort (313 cases and 2508 controls) to identify the optimal parameters based on predictive performance. We then tested the association between SSNS PRS and multiple clinical covariates in the independent European cohort. We then assessed PRS associations in the more clinically heterogeneous Nephrotic Syndrome Study Network (NEPTUNE) cohort.


239 children with SSNS from the independent European cohort also had clinical information. There was a significant negative correlation between PRS and age of onset (P=0.002) adjusting for sex and genetic principal components. There were no significant differences in the PRS between sexes or relapse patterns. We then generated PRS for 353 patients with focal segmental glomerulosclerosis or minimal change disease from NEPTUNE. The PRS was associated with age of onset (P=7.90x10-10) after adjustment for genetic ancestry, sex, and histology. Increasing PRS was significantly associated with increased odds of being child- vs adult- onset (adult onset ≥ 19 yrs; P=7.21x10-8).


This is the first study to create a PRS of NS. We used it to assess the relationship between PRS and NS phenotypes in two independent cohorts. Results suggest that individuals with increased genetic risk of disease have earlier onset. Future studies are needed to replicate our results and examine its predictive power.