Kidney Week

Abstract: TH-PO0631

Independent Effects of Family History and Polygenic Score in Predicting the Risk of CKD

Session Information

• Genetic Diseases of the Kidneys: Complex Kidney Traits
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Complex Kidney Traits

Authors

• Shang, Ning, Columbia University, New York, New York, United States

Ning Shang, PhD

• Khan, Atlas, Columbia University, New York, New York, United States

Atlas Khan, MS, PhD, FASN

• Kiryluk, Krzysztof, Columbia University, New York, New York, United States

Krzysztof Kiryluk, MD

Background

Family health history (FHH) and genetic predisposition contribute significantly to the risk of chronic kidney disease (CKD). However, their relative predictive values have not been systematically evaluated.

Methods

We analyzed preliminary data from a multi-center eMERGE IV cohort (N=4104) using Poisson regression models with a log link function and robust standard errors to estimate recurrence risk ratios (RRRs) for CKD associated with FHH and polygenic risk score (PRS). The CKD diagnosis and staging was defined electronically using our published e-phenotype. The PRS used was previously validated by our group. FHH was collected by self-report using MeTree software, and stratified by the number of affected relatives (single vs. multiple) and relatedness type (maternal, paternal, 1^st degree, 2^nd degree). All models were adjusted for age, sex, BMI, diabetes, hyperlipidemia, and site.

Results

Across all models, FHH was a strong and consistent predictor of CKD. Compared to individuals without a family history of CKD, those with at least one affected family member had a 1.56-fold to 6.73-fold increased risk of CKD across different definitions of FHH and CKD. The risk was similarly elevated or greater among those with two or more affected relatives, with RRRs ranging from 1.67 to 6.15 depending on CKD severity. Generally, the effect sizes for FHH became more pronounced for higher stages of CKD, suggesting that FHH is particularly predictive of more advanced disease. The PRS for CKD was also consistently associated with CKD, with statistically significant effects independent of FHH (RRR range: 1.05–1.11 per SD). We observed no significant interactions between the PRS and FHH.

Conclusion

Both FHH and PRS are independently associated with CKD risk. FHH had larger effects on the risk of more advanced CKD. Our findings support incorporating both familial and genetic information into the CKD risk stratification models.

Funding

• Other NIH Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025rs3pem8j