Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function

Kane E. Collins; Edmund Gilbert; Vincent Mauduit; Katherine A. Benson; Elhussein A.E. Elhassan; Conall O’Seaghdha; Claire Hill; Amy Jayne McKnight; Alexander P. Maxwell; Peter J. van der Most; Martin H. de Borst; Weihua Guan; Pamala A. Jacobson; Ajay K. Israni; Brendan J. Keating; Graham M. Lord; Salla Markkinen; Ilkka Helanterä; Kati Hyvärinen; Jukka Partanen; Stephen F. Madden; Matthew B. Lanktree; Sophie Limou; Gianpiero L. Cavalleri; Peter J. Conlon

doi:10.3389/ti.2025.14171

Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function

Kane E. Collins, Edmund Gilbert, Vincent Mauduit, Katherine A. Benson, Elhussein A.E. Elhassan, Conall O’Seaghdha, Claire Hill, Amy Jayne McKnight, Alexander P. Maxwell, Peter J. van der Most, Martin H. de Borst, Weihua Guan, Pamala A. Jacobson, Ajay K. Israni, Brendan J. Keating, Graham M. Lord, Salla Markkinen, Ilkka Helanterä, Kati Hyvärinen, Jukka PartanenStephen F. Madden, Matthew B. Lanktree, Sophie Limou, Gianpiero L. Cavalleri, Peter J. Conlon

Internal Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	14171
Journal	Transplant International
Volume	38
DOIs	https://doi.org/10.3389/ti.2025.14171
State	Published - 2025

Keywords

eGFR
graft function
graft survival
multivariable models
polygenic risk scores

ASJC Scopus subject areas

Transplantation

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10.3389/ti.2025.14171

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Collins, K. E., Gilbert, E., Mauduit, V., Benson, K. A., Elhassan, E. A. E., O’Seaghdha, C., Hill, C., McKnight, A. J., Maxwell, A. P., van der Most, P. J., de Borst, M. H., Guan, W., Jacobson, P. A., Israni, A. K., Keating, B. J., Lord, G. M., Markkinen, S., Helanterä, I., Hyvärinen, K., ... Conlon, P. J. (2025). Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function. Transplant International, 38, Article 14171. https://doi.org/10.3389/ti.2025.14171

Collins, KE, Gilbert, E, Mauduit, V, Benson, KA, Elhassan, EAE, O’Seaghdha, C, Hill, C, McKnight, AJ, Maxwell, AP, van der Most, PJ, de Borst, MH, Guan, W, Jacobson, PA, Israni, AK, Keating, BJ, Lord, GM, Markkinen, S, Helanterä, I, Hyvärinen, K, Partanen, J, Madden, SF, Lanktree, MB, Limou, S, Cavalleri, GL & Conlon, PJ 2025, 'Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function', Transplant International, vol. 38, 14171. https://doi.org/10.3389/ti.2025.14171

@article{707abc4163c044f88044fedbae3c083f,

title = "Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function",

abstract = "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.",

keywords = "eGFR, graft function, graft survival, multivariable models, polygenic risk scores",

author = "Collins, {Kane E.} and Edmund Gilbert and Vincent Mauduit and Benson, {Katherine A.} and Elhassan, {Elhussein A.E.} and Conall O{\textquoteright}Seaghdha and Claire Hill and McKnight, {Amy Jayne} and Maxwell, {Alexander P.} and {van der Most}, {Peter J.} and {de Borst}, {Martin H.} and Weihua Guan and Jacobson, {Pamala A.} and Israni, {Ajay K.} and Keating, {Brendan J.} and Lord, {Graham M.} and Salla Markkinen and Ilkka Helanter{\"a} and Kati Hyv{\"a}rinen and Jukka Partanen and Madden, {Stephen F.} and Lanktree, {Matthew B.} and Sophie Limou and Cavalleri, {Gianpiero L.} and Conlon, {Peter J.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2025 Collins, Gilbert, Mauduit, Benson, Elhassan, O{\textquoteright}Seaghdha, Hill, McKnight, Maxwell, van der Most, de Borst, Guan, Jacobson, Israni, Keating, Lord, Markkinen, Helanter{\"a}, Hyv{\"a}rinen, Partanen, Madden, Lanktree, Limou, Cavalleri and Conlon.",

year = "2025",

doi = "10.3389/ti.2025.14171",

language = "English (US)",

volume = "38",

journal = "Transplant International",

issn = "0934-0874",

publisher = "Frontiers Media SA",

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TY - JOUR

T1 - Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function

AU - Collins, Kane E.

AU - Gilbert, Edmund

AU - Mauduit, Vincent

AU - Benson, Katherine A.

AU - Elhassan, Elhussein A.E.

AU - O’Seaghdha, Conall

AU - Hill, Claire

AU - McKnight, Amy Jayne

AU - Maxwell, Alexander P.

AU - van der Most, Peter J.

AU - de Borst, Martin H.

AU - Guan, Weihua

AU - Jacobson, Pamala A.

AU - Israni, Ajay K.

AU - Keating, Brendan J.

AU - Lord, Graham M.

AU - Markkinen, Salla

AU - Helanterä, Ilkka

AU - Hyvärinen, Kati

AU - Partanen, Jukka

AU - Madden, Stephen F.

AU - Lanktree, Matthew B.

AU - Limou, Sophie

AU - Cavalleri, Gianpiero L.

AU - Conlon, Peter J.

N1 - Publisher Copyright: Copyright © 2025 Collins, Gilbert, Mauduit, Benson, Elhassan, O’Seaghdha, Hill, McKnight, Maxwell, van der Most, de Borst, Guan, Jacobson, Israni, Keating, Lord, Markkinen, Helanterä, Hyvärinen, Partanen, Madden, Lanktree, Limou, Cavalleri and Conlon.

PY - 2025

Y1 - 2025

N2 - 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.

AB - 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.

KW - eGFR

KW - graft function

KW - graft survival

KW - multivariable models

KW - polygenic risk scores

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UR - http://www.scopus.com/inward/citedby.url?scp=105000678593&partnerID=8YFLogxK

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DO - 10.3389/ti.2025.14171

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AN - SCOPUS:105000678593

SN - 0934-0874

VL - 38

JO - Transplant International

JF - Transplant International

M1 - 14171

ER -

Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function

Abstract

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