Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study

United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3

doi:10.1111/ajt.14594

Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study

United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3

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

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Abstract

Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.

Original language	English
Journal	American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Early online date	1 Feb 2018
DOIs	https://doi.org/10.1111/ajt.14594
Publication status	Published - Jun 2018

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10.1111/ajt.14594Licence: CC BY

Long- and short-term_FUENTES_Accepted 13 November 2018_ GOLD VoR (CC- BY)Final published version, 1.2 MBLicence: CC BY

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United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3 (2018). Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. https://doi.org/10.1111/ajt.14594

United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3. / Long- and short-term outcomes in renal allografts with deceased donors : A large recipient and donor genome-wide association study. In: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2018.

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title = "Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study",

abstract = "Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.",

author = "{United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3} and Hernandez-Fuentes, {Maria P} and Christopher Franklin and Irene Rebollo-Mesa and Jennifer Mollon and Florence Delaney and Esperanza Perucha and Caragh Stapleton and Richard Borrows and Catherine Byrne and Gianpiero Cavalleri and Brendan Clarke and Menna Clatworthy and John Feehally and Susan Fuggle and Gagliano, {Sarah A} and Sian Griffin and Abdul Hammad and Robert Higgins and Alan Jardine and Mary Keogan and Timothy Leach and Iain MacPhee and Mark, {Patrick B} and James Marsh and Peter Maxwell and William McKane and Adam McLean and Charles Newstead and Titus Augustine and Paul Phelan and Steve Powis and Peter Rowe and Neil Sheerin and Ellen Solomon and Henry Stephens and Raj Thuraisingham and Richard Trembath and Peter Topham and Robert Vaughan and Sacks, {Steven H} and Peter Conlon and Gerhard Opelz and Nicole Soranzo and Weale, {Michael E} and Lord, {Graham M}",

note = "{\textcopyright} 2018 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.",

year = "2018",

month = jun,

doi = "10.1111/ajt.14594",

language = "English",

journal = "American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons",

issn = "1600-6135",

publisher = "Wiley-Blackwell",

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United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3 2018, 'Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study', American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. https://doi.org/10.1111/ajt.14594

Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study. / United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3.
In: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 06.2018.

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

TY - JOUR

T1 - Long- and short-term outcomes in renal allografts with deceased donors

T2 - A large recipient and donor genome-wide association study

AU - United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3

AU - Hernandez-Fuentes, Maria P

AU - Franklin, Christopher

AU - Rebollo-Mesa, Irene

AU - Mollon, Jennifer

AU - Delaney, Florence

AU - Perucha, Esperanza

AU - Stapleton, Caragh

AU - Borrows, Richard

AU - Byrne, Catherine

AU - Cavalleri, Gianpiero

AU - Clarke, Brendan

AU - Clatworthy, Menna

AU - Feehally, John

AU - Fuggle, Susan

AU - Gagliano, Sarah A

AU - Griffin, Sian

AU - Hammad, Abdul

AU - Higgins, Robert

AU - Jardine, Alan

AU - Keogan, Mary

AU - Leach, Timothy

AU - MacPhee, Iain

AU - Mark, Patrick B

AU - Marsh, James

AU - Maxwell, Peter

AU - McKane, William

AU - McLean, Adam

AU - Newstead, Charles

AU - Augustine, Titus

AU - Phelan, Paul

AU - Powis, Steve

AU - Rowe, Peter

AU - Sheerin, Neil

AU - Solomon, Ellen

AU - Stephens, Henry

AU - Thuraisingham, Raj

AU - Trembath, Richard

AU - Topham, Peter

AU - Vaughan, Robert

AU - Sacks, Steven H

AU - Conlon, Peter

AU - Opelz, Gerhard

AU - Soranzo, Nicole

AU - Weale, Michael E

AU - Lord, Graham M

PY - 2018/6

Y1 - 2018/6

N2 - Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.

AB - Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.

U2 - 10.1111/ajt.14594

DO - 10.1111/ajt.14594

M3 - Article

C2 - 29392897

SN - 1600-6135

JO - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

JF - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

ER -

United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3. Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2018 Jun. Epub 2018 Feb 1. doi: 10.1111/ajt.14594

Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study

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