Kidney Week

Abstract: TH-PO0897

Multiancestry Genome-Wide Association Study for Kidney Transplant Outcomes in 15,695 Allograft Recipients

Session Information

• Transplantation: Basic Research
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2101 Transplantation: Basic

Authors

• Zanoni, Francesca, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardy, Italy

Francesca Zanoni, MD

• Rophina, Mercy, NYU Langone Health, New York, New York, United States

Mercy Rophina, PhD

• Israni, Ajay K., The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, United States

Ajay K. Israni, MD, MS

• Partanen, Jukka, Suomen Punainen Risti Veripalvelu, Vantaa, Uusimaa, Finland

Jukka Partanen, PhD

• Reindl-Schwaighofer, Roman, Medizinische Universitat Wien, Vienna, Austria

Roman Reindl-Schwaighofer, MD

• De Borst, Martin H., Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands

Martin H. De Borst, MD, PhD

• Bochud, Pierre-Yves, Centre Hospitalier Universitaire Vaudois, Lausanne, VD, Switzerland

Pierre-Yves Bochud, MD

• Limou, Sophie, Nantes Universite, Nantes, Pays de la Loire, France

Sophie Limou, PhD

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

Krzysztof Kiryluk, MD

• Keating, Brendan, NYU Langone Health, New York, New York, United States

Brendan Keating, PhD

Group or Team Name

• iGeneTRAiN Consortium.

Background

Kidney transplantation (KTx) is the optimal treatment for kidney failure, but achieving long-term graft survival remains a challenge. Identifying genetic determinants of acute rejection (AR) and graft failure (GF) may improve risk stratification. Herein, we conducted a multi-ancestry genome-wide association study (GWAS) meta-analysis to identify genetic variants associated with AR and GF.

Methods

A total of 15,695 KTx recipients from 16 global sites within the iGeneTRAiN Consortium were genome-wide genotyped and imputed using multi-ancestry reference panels. In each cohort, GWAS for biopsy-proven AR and death-censored GF were conducted. A Cox model adjusting for recipient/donor characteristics, transplant year, HLA mismatch, and genetic ancestry was constructed. GWAS was computed using linear mixed models with the residuals from the Cox analyses as outcomes. Results were meta-analyzed across cohorts under a fixed-effects model using common (MAF ≥1%), high quality (imputation R² ≥0.8) variants shared by ≥5 cohorts.

Results

The multi-ancestry meta-analysis across 16 cohorts included 10,941,846 SNPs for time-to-AR (λgc = 1.01) and 10,990,144 SNPs for time-to-GF (λgc = 1.01). A genome-wide significant association for time-to-AR was observed on chromosome 18 (Fig.1). The top SNP, rs72958239 (effect allele: T, beta (se)=-0.02 (0.003), p=3.4x10^-8), is a variant located near DSEL, a gene involved in dermatan sulfate biosynthesis that plays a role in cell signaling, proliferation, and differentiation. DSEL is expressed by proximal tubules and kidney fibroblasts. Other suggestive signals (p<10^-5) associated with AR and GF map to genes involved in immune regulation, cellular metabolism, and tumor suppression.

Conclusion

We report the largest multi-ancestry GWAS meta-analysis for kidney transplantation outcomes. Our analyses identified a novel risk locus for AR, and prioritized several suggestive loci for follow-up studies.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025qn0d3g2b