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Design and Implementation of the International Genetics and Translational Research in Transplantation Network

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...

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Detalles Bibliográficos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623847/
https://www.ncbi.nlm.nih.gov/pubmed/26479416
http://dx.doi.org/10.1097/TP.0000000000000913
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collection PubMed
description 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 16494 transplant recipients and 11669 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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spelling pubmed-46238472015-11-20 Design and Implementation of the International Genetics and Translational Research in Transplantation Network Transplantation Original Clinical Science—General 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 16494 transplant recipients and 11669 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. Lippincott Williams & Wilkins 2015-11 2015-11-04 /pmc/articles/PMC4623847/ /pubmed/26479416 http://dx.doi.org/10.1097/TP.0000000000000913 Text en Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
spellingShingle Original Clinical Science—General
Design and Implementation of the International Genetics and Translational Research in Transplantation Network
title Design and Implementation of the International Genetics and Translational Research in Transplantation Network
title_full Design and Implementation of the International Genetics and Translational Research in Transplantation Network
title_fullStr Design and Implementation of the International Genetics and Translational Research in Transplantation Network
title_full_unstemmed Design and Implementation of the International Genetics and Translational Research in Transplantation Network
title_short Design and Implementation of the International Genetics and Translational Research in Transplantation Network
title_sort design and implementation of the international genetics and translational research in transplantation network
topic Original Clinical Science—General
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623847/
https://www.ncbi.nlm.nih.gov/pubmed/26479416
http://dx.doi.org/10.1097/TP.0000000000000913