Donor and recipient polygenic risk scores influence kidney transplant function
Kidney transplant outcomes are influenced by donor and recipient age, sex, HLA mismatch, donor type, anti-rejection medication adherence and disease recurrence, but variability in transplant outcomes remains unexplained. We hypothesise that donor and recipient polygenic burden for traits related to kidney function may also influence graft function. We assembled a cohort of 6,060 living and deceased kidney donor-recipient pairs. We calculated polygenic risk scores (PRSs) for kidney function-related traits in both donors and recipients. We investigated the association between these PRSs and recipient eGFR at 1- and 5-year post-transplant as well as graft failure. Donor: hypertension PRS (P < 0.001), eGFR PRS (P < 0.001), and intracranial aneurysm PRS (P = 0.01), along with recipient eGFR PRS (P = 0.001) were associated with eGFR at 1-year post-transplantation. Clinical factors explained 25% of the variation in eGFR at 1-year and 13% at 5-year, with PRSs cumulatively adding 1% in both cases. PRSs were not associated with long-term graft survival. We demonstrate a small, but statistically significant association between donor and recipient PRSs and recipient graft function at 1- and 5-year post-transplant. This effect is, at present, unlikely to have clinical application and further research is required to improve PRS performance.
Funding
Royal College of Surgeons in Ireland StAR PhD
NIH/NIAID grants 5U19-AI070119 and 5U01-AI058013
Genetic Variants Associated with Tacrolimus Metabolism in Kidney Transplant Recipients
National Institute of Allergy and Infectious Diseases
Find out more...Government of Finland VTR funding, Munuaissäätiö
Suomen Transplantaatiokirurginen yhdistys ry
Academy of Finland
Etoiles Montantes funding by the Pays de la Loire region (no 2018-09998)
IRCT Dialyse research project by the Société Francophone de Néphrologie, Dialyse et Transplantation (SFNDT)
Greffe research project by French Agence de la Biomédecine (ABM, no 18GREFFE014)
Roche Pharma
Novartis
Astellas
Chiesi
Sandoz and Sanofi laboratories
HSC R&D division (STL/5569/19)
Social Circumstances and Epigenomics Promoting Health in Three Countries
Medical Research Council
Find out more...Discovery of an integrated risk profile for chronic kidney disease and development of a clinical biomarker panel for personalising medicine
Science Foundation Ireland
Find out more...The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) - CAPI
Economic and Social Research Council
Find out more...Astellas BV.
Defining the genetic basis of the interactions between donor and recipient DNA that determine early and late renal transplant dysfunction.
Wellcome Trust
Find out more...Wellcome Trust "WTCCC3”
Defining the cellular and molecular pathogenesis of ulcerative colitis
Medical Research Council
Find out more...The role of the immune cell transcription factor T-bet in metabolic physiology and pathophysiology.
Medical Research Council
Find out more...Medical Research Council (G0801537/ID: 88245)
Guy’s and St Thomas’ Charity (grants R080530 and R090782)
European Union FP7 (grant agreement no HEALTHF5–2010–260687. and project number 305147: BIO-DrIM)
National Institute for Health Research Biomedical Research Centre at Guy’s and St Thomas’ and King’s College London
History
Data Availability Statement
The data analyzed in this study is subject to the following licenses/restrictions: Privacy concerns prevent these datasets being made publicly available. Requests to access these datasets should be directed to Graham Lord, graham.lord@manchester.ac.uk.Comments
The original article is available at https://www.frontierspartnerships.org/Published Citation
Collins KE, et al. Donor and recipient polygenic risk scores influence kidney transplant function. Transpl Int. 2025;38:14171.Publication Date
4 March 2025External DOI
PubMed ID
40104404Department/Unit
- Beaumont Hospital
- Data Science Centre
- Medicine
- School of Pharmacy and Biomolecular Sciences
- FutureNeuro Centre
- School of Population Health
Publisher
Frontiers Media SAVersion
- Published Version (Version of Record)
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