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

Author

Keating, Brendan J., van Setten, Jessica, Jacobson, Pamala A., Holmes, Michael V., Verma, Shefali S., Chandrupatla, Hareesh R., Nair, Nikhil, Gao, Hui, Li, Yun R., Chang, Bao-Li, Wong, Chanel, Phillips, Randy, Cole, Brian S., Mukhtar, Eyas, Zhang, Weijia, Cao, Hongzhi, Mohebnasab, Maede, Hou, Cuiping, Lee, Takesha, Steel, Laura, Shaked, Oren, Garifallou, James, Miller, Michael B., Karczewski, Konrad J., Akdere, Abdullah, Gonzalez, Ana, Lloyd, Kelsey M., McGinn, Daniel, Michaud, Zach, Colasacco, Abigail, Lek, Monkol, Fu, Yao, Pawashe, Mayur, Guettouche, Toumy, Himes, Aubree, Perez, Leat, Guan, Weihua, Wu, Baolin, Schladt, David, Menon, Madhav, Zhang, Zhongyang, Tragante, Vinicius, de Jonge, Nicolaas, Otten, Henny G., de Weger, Roel A., van de Graaf, Ed A., Baan, Carla C., Manintveld, Olivier C., De Vlaminck, Iwijn, Piening, Brian D., Strehl, Calvin, Shaw, Mary, Snieder, Harold, Klintmalm, Goran B., O'Leary, Jacqueline G., Amaral, Sandra, Goldfarb, Samuel, Rand, Elizabeth, Rossano, Joseph W., Kohli, Utkarsh, Heeger, Peter, Stahl, Eli, Christie, Jason D., Fuentes, Maria Hernandez, Levine, John E., Aplenc, Richard, Schadt, Eric E., Stranger, Barbara E., Kluin, Jolanda, Potena, Luciano, Zuckermann, Andreas, Khush, Kiran, Alzahrani, Alhusain J., Al-Muhanna, Fahad A., Al-Ali, Amein K., Al-Ali, Rudaynah, Al-Rubaish, Abdullah M., Al-Mueilo, Samir, Byrne, Edna M., Miller, David, Alexander, Stephen I., Onengut-Gumuscu, Suna, Rich, Stephen S., Suthanthiran, Manikkam, Tedesco, Helio, Saw, Chee L., Ragoussis, Jiannis, Kfoury, Abdallah G., Horne, Benjamin, Carlquist, John, Gerstein, Mark B., Reindl-Schwaighofer, Roman, Oberbauer, Rainer, Wijmenga, Cisca, Palmer, Scott, Pereira, Alexandre C., Segovia, Javier, Alonso-Pulpon, Luis A., Comez-Bueno, Manuel, Vilches, Carlos, Jaramillo, Natalia, de Borst, Martin H., Naesens, Maarten, Hao, Ke, MacArthur, DanielG., Balasubramanian, Suganthi, Conlon, Peter J., Lord, Graham M., Ritchie, Marylyn D., Snyder, Michael, Olthoff, Kim M., Moore, Jason H., Petersdorf, Effie W., Kamoun, Malek, Wang, Jun, Monos, Dimitri S., de Bakker, Paul I. W., Hakonarson, Hakon, Murphy, Barbara, Lankree, Matthew B., Garcia-Pavia, Pablo, Oetting, William S., Birdwell, Kelly A., Bakker, Stephan J. L., Israni, Ajay K., Shaked, Abraham, Asselbergs, Folkert W., Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Kidney Center (GKC), Lifestyle Medicine (LM), Vascular Ageing Programme (VAP), Groningen Institute for Organ Transplantation (GIOT), Gastroenterology & Hepatology, Dermatology, Erasmus MC other, Internal Medicine, Cardiology, and Cardiothoracic Surgery

Subjects
Graft Rejection, International Cooperation, Genome-wide association study, 030230 surgery, VARIANTS, Organ transplantation, Organizational, Translational Research, Biomedical, 0302 clinical medicine, Models, Risk Factors, Databases, Genetic, Medicine, CARDIAC TRANSPLANTATION, Cooperative Behavior, Non-U.S. Gov't, Translational Medical Research, Genetics, 0303 health sciences, Research Support, Non-U.S. Gov't, Graft Survival, Single Nucleotide, Original Clinical Science—General, 3. Good health, GENOTYPE, surgical procedures, operative, Phenotype, Treatment Outcome, Research Design, Genetic Markers, medicine.medical_specialty, Primary Graft Dysfunction, Translational research, Human leukocyte antigen, Research Support, DONOR, Polymorphism, Single Nucleotide, N.I.H, 03 medical and health sciences, Databases, Genetic, SDG 3 - Good Health and Well-being, Research Support, N.I.H., Extramural, Journal Article, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, PRIMARY GRAFT DYSFUNCTION, Genetic Association Studies, 030304 developmental biology, Genetic association, Transplantation, business.industry, ELECTRONIC MEDICAL-RECORDS, Extramural, Organ Transplantation, Genetic architecture, POLYMORPHISM, RECIPIENTS, Models, Organizational, Sample Size, KIDNEY ALLOGRAFT FUNCTION, business
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 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., iGeneTRAiN is a consortium that has genome-wide genotype datasets. These genomic data allows robust statistically analysis of genetic associations that impact graft and patients variables such as, such as: graft survival, acute rejection, new onset of diabetes after transplantation, and delayed graft kidney function. Supplemental digital content is available in the text.

Published
2015
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