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

Brendan J. Keating, Jessica Van Setten, Pamala A. Jacobson, Michael V. Holmes, Shefali S. Verma, Hareesh R. Chandrupatla, Nikhil Nair, Hui Gao, Yun R. Li, Bao Li Chang, Chanel Wong, Randy Phillips, Brian S. Cole, Eyas Mukhtar, Weijia Zhang, Hongzhi Cao, Maede Mohebnasab, Cuiping Hou, Takesha Lee, Laura SteelOren Shaked, James Garifallou, Michael B. Miller, Konrad J. Karczewski, Abdullah Akdere, Ana Gonzalez, Kelsey M. Lloyd, Daniel McGinn, Zach Michaud, Abigail Colasacco, Monkol Lek, Yao Fu, Mayur Pawashe, Toumy Guettouche, Aubree Himes, Leat Perez, Weihua Guan, Baolin Wu, David Schladt, Madhav Menon, Zhongyang Zhang, Vinicius Tragante, Nicolaas De Jonge, Henny G. Otten, Roel A. De Weger, Ed A. Van De Graaf, Carla C. Baan, Olivier C. Manintveld, Iwijn De Vlaminck, William S. Oetting, The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN)

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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

Bibliographical note

Publisher Copyright:
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

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