Conference Proceeding

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

Dr. Brendan Keating,
Faculty, Institute of Translational Medicine, USA

Brendan Keating received his D.Phil. (Ph.D.) in molecular genetics from the Department of Clinical Medicine at University of Oxford, UK. He completed a post-doctoral fellowship at the Institute of Translational Medicine and Therapeutics at UPenn, and was a visiting Scientist at the Welcome Trust Sanger Institute, Cambridge, UK. Dr. Keating has designed and developed genomic tools for cardiovascular related studies resulting in over a hundred genetic discoveries in various metabolic and CVD-related traits. Dr. Keating joined the Faculty at Penn in 2012, and recently moved his primary appointment to the Division of Transplantation.

To date over 650,000 solid-organ transplants have been conducted in the United States alone with estimates of approximately 4 million transplants performed worldwide. Most recipientsare subjected to potent immunosuppression therapies (ISTs) for the remainder of their lives. While there have been considerable advances in graft clinical management, and ISTs over the last two decades, the rates of acute rejection are still significant, and co-morbidities from ISTs such as new onset of diabetes after transplant (NODAT), nephrotoxicity and liver damage remain major clinical issues. With the increase in malaise such as chronic kidney disease and congestive heart failure - waiting lists for donor organs continue to expand above-and-beyond the pool of available organ donations. While HLA compatibility is recognized as being very important for graft survival, an increasing body of evidence shows that non-HLA allogenicity accounts for over twice that of HLA in kidney transplantations. Despite the high mortality, comorbidities and monetary costs associated with transplantation it has only recently become an active area for collaboration in genomics. Well-powered genome-wide association studies (GWAS) are now available from The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN) which is conducting meta-analyses for various transplant-related phenotypes across >40,500 recipients/donors from 28 transplant studies across Europe, North America and Australia. We describe meta-analyses for the first five major phenotypes in iGeneTRAiN: acute rejection; graft survival; new onset of diabetes after transplantation (NODAT); delayed graft function (DGF) and patient survival. We also describe GWAS meta-analyses for tacrolimus levels in African American and European ancestry transplant recipients across 11 studies. We also describe a number of highly specific and sensitive non-invasive miRNA and mRNA biomarker panels for detection of sub-clinical rejection by iGeneTRAiN studies which are approaching implementation in the clinic.

Published: 28 April 2017