Kidney Week

Abstract: FR-PO0728

Genome-Wide Association Study of Fibroblast Growth Factor 23 (FGF-23) in the CKD in Children (CKiD) Study

Session Information

• Pediatric Nephrology: CKD, ESKD, and Glomerular Diseases
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1900 Pediatric Nephrology

Authors

• Lee, Arthur M, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Arthur M Lee, MD

• March, Michael E., The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Michael E. March, PhD

• Roem, Jennifer, Johns Hopkins University, Baltimore, Maryland, United States

Jennifer Roem, MS

• Wong, Craig S., University of New Mexico, Albuquerque, New Mexico, United States

Craig S. Wong, MD, MPH

• Warady, Bradley A., Children's Mercy Kansas City, Kansas City, Missouri, United States

Bradley A. Warady, MD

• Furth, Susan L., The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Susan L. Furth, MD, PhD

• Denburg, Michelle, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Michelle Denburg, MD

• Robinson-Cohen, Cassianne, Vanderbilt University, Nashville, Tennessee, United States

Cassianne Robinson-Cohen, PhD, FASN

• Perwad, Farzana, University of California San Francisco, San Francisco, California, United States

Farzana Perwad, MD

Background

Genetic variation influences circulating FGF23 in adults with CKD, but little is known in pediatric populations. We aimed to identify SNPs associated with FGF23 in children with CKD.

Methods

CKiD is a multicenter cohort of children with CKD. Participants with FGF23 and genome-wide genotyping data (Illumina Omni2.5) were included. Data were filtered to exclude SNPs with call rate<95%, minor allele frequency (MAF)<1%, or individuals missing >2% of SNPs. Imputation used the TOPMed reference panel. Post-imputation, SNPs with MAF≥5% were retained if R2≥0.3; SNPs with MAF≥1% were retained if R2≥0.5.
Linear regression assessed log-FGF23 on SNP dosage, adjusted for age, sex, log-eGFR, and the first 10 genetic principal components (Model 1). Genome-wide significance was defined as p<5×10^-8. Significant SNPs were carried forward and additionally adjusted for serum calcium, phosphorus, intact PTH, and 25(OH)D (all log-transformed) (Model 2).

Results

586 participants were included, with median [IQR] age of 12 [8-15] years and eGFR of 51 [37-65] ml/min/1.73m². We discovered 9 independent significant FGF23-SNP associations in protein-encoding regions: VAV3 (involved in cytoskeletal remodeling), NPSR1 (vasopressin subfamily G-protein coupled receptor), ANK1 (cytoskeletal membrane protein), SHANK2 (scaffolding protein), and KLHL36 (Kelch-like protein involved in protein ubiquitination). All loci remained significant after adjustment for other mineral metabolites (Table 1).

Conclusion

We identified novel, genome-wide significant associations between FGF23 and SNPs in protein-coding genes in children with CKD. SHANK2 mediates renal tubular phosphate transport through microtubule-dependent mechanisms. These findings extend prior work in adults, highlight potential pediatric-specific genetic FGF23 regulation, and suggest new avenues to investigate mineral metabolism disorders in children with CKD.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025wpzcw789