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

Keating, BJ and Van Setten, J and Jacobson, PA and Holmes, MV and Verma, SS and Chandrupatla, HR and Nair, N and Gao, H and Li, YR and Chang, BL and Wong, C and Phillips, R and Cole, BS and Mukhtar, E and Zhang, W and Cao, H and Mohebnasab, M and Hou, C and Lee, T and Steel, L and Shaked, O and Garifallou, J and Miller, MB and Karczewski, KJ and Akdere, A and Gonzalez, A and Lloyd, KM and McGinn, D and Michaud, Z and Colasacco, A and Lek, M and Fu, Y and Pawashe, M and Guettouche, T and Himes, A and Perez, L and Guan, W and Wu, B and Schladt, D and Menon, M and Zhang, Z and Tragante, V and De Jonge, N and Otten, HG and De Weger, RA and Van De Graaf, EA and Baan, CC and Manintveld, OC and De Vlaminck, I and Piening, BD and Strehl, C and Shaw, M and Snieder, H and Klintmalm, GB and O'Leary, JG and Amaral, S and Goldfarb, S and Rand, E and Rossano, JW and Kohli, U and Heeger, P and Stahl, E and Christie, JD and Fuentes, MH and Levine, JE and Aplenc, R and Schadt, EE and Stranger, BE and Kluin, J and Potena, L and Zuckermann, A and Khush, K and Alzahrani, AJ and Al-Muhanna, FA and Al-Ali, AK and Al-Ali, R and Al-Rubaish, AM and Al-Mueilo, S and Byrne, EM and Miller, D and Alexander, SI and Onengut-Gumuscu, S and Rich, SS and Suthanthiran, M and Tedesco, H and Saw, CL and Ragoussis, J and Kfoury, AG and Horne, B and Carlquist, J and Gerstein, MB and Reindl-Schwaighofer, R and Oberbauer, R and Wijmenga, C and Palmer, S and Pereira, AC and Segovia, J and Alonso-Pulpon, LA and Comez-Bueno, M and Vilches, C (2015) Design and implementation of the international genetics and translational research in transplantation network. Transplantation, 99 (11). 2401 - 2412. ISSN 0041-1337

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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.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Keating, BJ Van Setten, J Jacobson, PA Holmes, MV Verma, SS Chandrupatla, HR Nair, N Gao, H Li, YR Chang, BL Wong, C Phillips, R Cole, BS Mukhtar, E Zhang, W Cao, H Mohebnasab, M MAM1236@pitt.edu MAM1236 0000-0001-6623-9514 Hou, C Lee, T Steel, L Shaked, O Garifallou, J Miller, MB Karczewski, KJ Akdere, A Gonzalez, A Lloyd, KM McGinn, D Michaud, Z Colasacco, A Lek, M Fu, Y Pawashe, M Guettouche, T Himes, A Perez, L Guan, W Wu, B Schladt, D Menon, M Zhang, Z Tragante, V De Jonge, N Otten, HG De Weger, RA Van De Graaf, EA Baan, CC Manintveld, OC De Vlaminck, I Piening, BD Strehl, C Shaw, M Snieder, H Klintmalm, GB O'Leary, JG Amaral, S Goldfarb, S Rand, E Rossano, JW Kohli, U Heeger, P Stahl, E Christie, JD Fuentes, MH Levine, JE Aplenc, R Schadt, EE Stranger, BE Kluin, J Potena, L Zuckermann, A Khush, K Alzahrani, AJ Al-Muhanna, FA Al-Ali, AK Al-Ali, R Al-Rubaish, AM Al-Mueilo, S Byrne, EM Miller, D Alexander, SI Onengut-Gumuscu, S Rich, SS Suthanthiran, M Tedesco, H Saw, CL Ragoussis, J Kfoury, AG Horne, B Carlquist, J Gerstein, MB Reindl-Schwaighofer, R Oberbauer, R Wijmenga, C Palmer, S Pereira, AC Segovia, J Alonso-Pulpon, LA Comez-Bueno, M Vilches, C
Date:	23 October 2015
Date Type:	Publication
Journal or Publication Title:	Transplantation
Volume:	99
Number:	11
Page Range:	2401 - 2412
DOI or Unique Handle:	10.1097/tp.0000000000000913
Schools and Programs:	School of Medicine > Pathology
Refereed:	Yes
ISSN:	0041-1337
Date Deposited:	29 Aug 2022 15:39
Last Modified:	06 Sep 2022 13:55
URI:	http://d-scholarship.pitt.edu/id/eprint/43676

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