Design and implementation of the international genetics and translational research in transplantation network

The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN)

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background. Genetic association studies of transplantation outcomes have been hampered by small samples and highly complex multifactorial phenotypes, hindering investigations of the genetic architecture of a range of comorbidities which significantly impact graft and recipient life expectancy. We describe here the rationale and design of the International Genetics & Translational Research in Transplantation Network. The network comprises 22 studies to date, including 16 494 transplant recipients and 11 669 donors, of whom more than 5000 are of non-European ancestry, all of whom have existing genomewide genotype data sets. Methods. We describe the rich genetic and phenotypic information available in this consortium comprising heart, kidney, liver, and lung transplant cohorts. Results. We demonstrate significant power in International Genetics & Translational Research in Transplantation Network to detect main effect association signals across regions such as the MHC region as well as genomewide for transplant outcomes that span all solid organs, such as graft survival, acute rejection, new onset of diabetes after transplantation, and for delayed graft function in kidney only. Conclusions. This consortium is designed and statistically powered to deliver pioneering insights into the genetic architecture of transplant-related outcomes across a range of different solid-organ transplant studies. The study design allows a spectrum of analyses to be performed including recipient-only analyses, donor-recipient HLA mismatches with focus on loss-of-function variants and nonsynonymous single nucleotide polymorphisms.

Original languageEnglish (US)
Pages (from-to)2401-2412
Number of pages12
JournalTransplantation
Volume99
Issue number11
DOIs
StatePublished - Oct 23 2015

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Genetic Research
Translational Medical Research
Transplantation
Transplants
Tissue Donors
Delayed Graft Function
Kidney
Genetic Association Studies
Graft Survival
Life Expectancy
Single Nucleotide Polymorphism
Comorbidity
Spectrum Analysis
Genotype
Phenotype
Lung
Liver

ASJC Scopus subject areas

  • Transplantation

Cite this

The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN) (2015). Design and implementation of the international genetics and translational research in transplantation network. Transplantation, 99(11), 2401-2412. https://doi.org/10.1097/TP.0000000000000913

Design and implementation of the international genetics and translational research in transplantation network. / The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN).

In: Transplantation, Vol. 99, No. 11, 23.10.2015, p. 2401-2412.

Research output: Contribution to journalArticle

The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN) 2015, 'Design and implementation of the international genetics and translational research in transplantation network', Transplantation, vol. 99, no. 11, pp. 2401-2412. https://doi.org/10.1097/TP.0000000000000913
The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN). Design and implementation of the international genetics and translational research in transplantation network. Transplantation. 2015 Oct 23;99(11):2401-2412. https://doi.org/10.1097/TP.0000000000000913
The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN). / Design and implementation of the international genetics and translational research in transplantation network. In: Transplantation. 2015 ; Vol. 99, No. 11. pp. 2401-2412.
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abstract = "Background. Genetic association studies of transplantation outcomes have been hampered by small samples and highly complex multifactorial phenotypes, hindering investigations of the genetic architecture of a range of comorbidities which significantly impact graft and recipient life expectancy. We describe here the rationale and design of the International Genetics & Translational Research in Transplantation Network. The network comprises 22 studies to date, including 16 494 transplant recipients and 11 669 donors, of whom more than 5000 are of non-European ancestry, all of whom have existing genomewide genotype data sets. Methods. We describe the rich genetic and phenotypic information available in this consortium comprising heart, kidney, liver, and lung transplant cohorts. Results. We demonstrate significant power in International Genetics & Translational Research in Transplantation Network to detect main effect association signals across regions such as the MHC region as well as genomewide for transplant outcomes that span all solid organs, such as graft survival, acute rejection, new onset of diabetes after transplantation, and for delayed graft function in kidney only. Conclusions. This consortium is designed and statistically powered to deliver pioneering insights into the genetic architecture of transplant-related outcomes across a range of different solid-organ transplant studies. The study design allows a spectrum of analyses to be performed including recipient-only analyses, donor-recipient HLA mismatches with focus on loss-of-function variants and nonsynonymous single nucleotide polymorphisms.",
author = "{The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN)} and Keating, {Brendan J.} and {Van Setten}, Jessica and Jacobson, {Pamala A.} and Holmes, {Michael V.} and Verma, {Shefali S.} and Chandrupatla, {Hareesh R.} and Nikhil Nair and Hui Gao and Li, {Yun R.} and Chang, {Bao Li} and Chanel Wong and Randy Phillips and Cole, {Brian S.} and Eyas Mukhtar and Weijia Zhang and Hongzhi Cao and Maede Mohebnasab and Cuiping Hou and Takesha Lee and Laura Steel and Oren Shaked and James Garifallou and Miller, {Michael B.} and Karczewski, {Konrad J.} and Abdullah Akdere and Ana Gonzalez and Lloyd, {Kelsey M.} and Daniel McGinn and Zach Michaud and Abigail Colasacco and Monkol Lek and Yao Fu and Mayur Pawashe and Toumy Guettouche and Aubree Himes and Leat Perez and Weihua Guan and Baolin Wu and David Schladt and Madhav Menon and Zhongyang Zhang and Vinicius Tragante and {De Jonge}, Nicolaas and Otten, {Henny G.} and {De Weger}, {Roel A.} and {Van De Graaf}, {Ed A.} and Baan, {Carla C.} and Manintveld, {Olivier C.} and {De Vlaminck}, Iwijn and O'Leary, {Jacqueline G.}",
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AU - Keating, Brendan J.

AU - Van Setten, Jessica

AU - Jacobson, Pamala A.

AU - Holmes, Michael V.

AU - Verma, Shefali S.

AU - Chandrupatla, Hareesh R.

AU - Nair, Nikhil

AU - Gao, Hui

AU - Li, Yun R.

AU - Chang, Bao Li

AU - Wong, Chanel

AU - Phillips, Randy

AU - Cole, Brian S.

AU - Mukhtar, Eyas

AU - Zhang, Weijia

AU - Cao, Hongzhi

AU - Mohebnasab, Maede

AU - Hou, Cuiping

AU - Lee, Takesha

AU - Steel, Laura

AU - Shaked, Oren

AU - Garifallou, James

AU - Miller, Michael B.

AU - Karczewski, Konrad J.

AU - Akdere, Abdullah

AU - Gonzalez, Ana

AU - Lloyd, Kelsey M.

AU - McGinn, Daniel

AU - Michaud, Zach

AU - Colasacco, Abigail

AU - Lek, Monkol

AU - Fu, Yao

AU - Pawashe, Mayur

AU - Guettouche, Toumy

AU - Himes, Aubree

AU - Perez, Leat

AU - Guan, Weihua

AU - Wu, Baolin

AU - Schladt, David

AU - Menon, Madhav

AU - Zhang, Zhongyang

AU - Tragante, Vinicius

AU - De Jonge, Nicolaas

AU - Otten, Henny G.

AU - De Weger, Roel A.

AU - Van De Graaf, Ed A.

AU - Baan, Carla C.

AU - Manintveld, Olivier C.

AU - De Vlaminck, Iwijn

AU - O'Leary, Jacqueline G.

PY - 2015/10/23

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N2 - Background. Genetic association studies of transplantation outcomes have been hampered by small samples and highly complex multifactorial phenotypes, hindering investigations of the genetic architecture of a range of comorbidities which significantly impact graft and recipient life expectancy. We describe here the rationale and design of the International Genetics & Translational Research in Transplantation Network. The network comprises 22 studies to date, including 16 494 transplant recipients and 11 669 donors, of whom more than 5000 are of non-European ancestry, all of whom have existing genomewide genotype data sets. Methods. We describe the rich genetic and phenotypic information available in this consortium comprising heart, kidney, liver, and lung transplant cohorts. Results. We demonstrate significant power in International Genetics & Translational Research in Transplantation Network to detect main effect association signals across regions such as the MHC region as well as genomewide for transplant outcomes that span all solid organs, such as graft survival, acute rejection, new onset of diabetes after transplantation, and for delayed graft function in kidney only. Conclusions. This consortium is designed and statistically powered to deliver pioneering insights into the genetic architecture of transplant-related outcomes across a range of different solid-organ transplant studies. The study design allows a spectrum of analyses to be performed including recipient-only analyses, donor-recipient HLA mismatches with focus on loss-of-function variants and nonsynonymous single nucleotide polymorphisms.

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