Abstract: TH-PO0713
Mendelian Randomization Identifies Circulating Plasma Proteins as Biomarkers for Steroid-Sensitive Nephrotic Syndrome
Session Information
- Glomerular Innovations: Artificial Intelligence, Multiomics, and Biomarkers
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Heydari, Daniel, McGill University, Montreal, Quebec, Canada
- Downie, Mallory Lorraine, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
Background
Steroid-sensitive nephrotic syndrome (SSNS) is the most common glomerular disease in children worldwide. The pathogenesis of SSNS is unknown, limiting us to non-specific treatments that have a heavy burden of side effects. Genome-wide association studies (GWAS) have identified several immunogenetic loci associated with disease, but have not identified causal variants or etiologic pathways, which limits our ability to provide targeted treatment to patients. Novel validated targets for the development of non-toxic treatments of SSNS are needed. One source of such targets is circulating plasma proteins. We aimed to identify plasma proteins associated with SSNS in European individuals using a Mendelian randomization (MR) approach.
Methods
Using eight large proteomic GWAS from 119252 European individuals, we selected cis genetic determinants of 3833 plasma proteins in adults and 1216 proteins in children. We screened these proteins for causal associations with SSNS using two-sample MR in 422 European pediatric SSNS cases and 5642 control subjects. We then colocalized significantly associated proteins using HLAcoloc.
Results
We tested 1628 unique proteins in adults and 210 proteins in children, and we found four plasma proteins significantly associated with SSNS (HLA-E: p=2.95e-7, Odds Ratio [OR]=8.17, Confidence Intervals [CI] 3.66-18.25; C4A: p=1.63e-6, [OR]=0.12, [CI] 0.05-0.29; APOM: p=1.37e-5, [OR]=0.40, [CI] 0.27-0.61 ; TNXB: p=2.95e-4, [OR]=0.49, [CI] 0.33-0.72). Two of these proteins successully colocalized using HLAcoloc (TNXB, 100% probability at HLA-C; APOM, 97% probability at HLA-DRB1).
Conclusion
We identified four novel plasma proteins associated with SSNS, two of which colocalized. Our findings support a potential utility of these proteins as targets for development or repositioning of drugs to treat SSNS.