Genome-Wide Study Updates in The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN)
- 1Division of Transplantation Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, United States
- 2Department of Cardiology, University Medical Center Utrecht, Netherlands
- 3Department of Nephrology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, United States
- 4Immunogenetics and Biology of Transplantation Unit, University Hospital of the City of Health and Science of Turin, Italy
- 5Division of Medical Genetics, Department of Medical Sciences, School of Medicine, University of Turin, Italy
- 6Department of Hospital Pharmacy, University Medical Center Rotterdam, Netherlands
- 7Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, South Korea
- 8Division of Nephrology, Department of Medicine, University of Toronto, Canada
The prevalence of end-stage renal disease (ESRD) and the number of kidney transplants performed continues to rise every year, straining the procurement of deceased and living kidney allografts and health systems. Genome-wide genotyping and sequencing of diseased populations have uncovered genetic contributors in substantial proportions of ESRD patients. A number of these discoveries are beginning to be utilized in risk stratification and clinical management of patients. Specifically, genetics can provide insight into the primary cause of chronic kidney disease (CKD), the risk of progression to ESRD, and post-transplant outcomes, including various forms of allograft rejection. The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN), is a multi-site consortium that encompasses > 45 genetic studies with genome-wide genotyping from over 51,000 transplant samples, including genome-wide data from > 30 kidney transplant cohorts (n=28,015). iGeneTRAiN is statistically powered to capture both rare and common genetic contributions to ESRD and post-transplant outcomes. Determining the primary cause of ESRD is often difficult to ascertain especially where formal biopsy diagnosis is not performed, and is unavailable in ~2% to > 20% of kidney transplant recipients in iGeneTRAiN studies. We overview our current copy number variant (CNV) screening approaches from genome-wide genotyping datasets in iGeneTRAiN, in attempts to discover and validate genetic contributors to CKD and ESRD. Greater aggregation and analyses of well phenotyped patients with genome-wide datasets will undoubtedly yield insights into the underlying pathophysiological mechanisms of CKD, leading the way to improved diagnostic precision in nephrology.
Keywords: Genomics, kidney disease, GWAS, whole exome analysis, whole genome sequencing
Received: 26 Mar 2019;
Accepted: 09 Oct 2019.
Copyright: © 2019 Fishman, Mohebnasab, Van Setten, Zanoni, Wang, Deaglio, Amoroso, van Gelder, Lee, Kiryluk, Lanktree and Keating. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Brendan Keating, Division of Transplantation Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States, firstname.lastname@example.org