Genome-Wide Study Updates in the International Genetics and Translational Research in Transplantation Network (iGeneTRAiN)

Abstract

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. 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.

Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

“…101 Accordingly, success has been limited in identifying common kidney disease susceptibility variants in individual observational studies of adult [102][103][104][105] and pediatric [106][107][108] CKD. Conference participants therefore recognized the importance of collaborative consortia, such as the Chronic Kidney Disease Genetics Consortium (CKDGen), 11,109 Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, 66,110 International Genetics & Translational Research in Transplantation Network (iGeneTRAiN), 111 and Continental Origins and Genetic Epidemiology Network (COGENT) Kidney Consortium, 112,113 that aggregate and harmonize genetic and phenotypic data across multiple studies for combined genetic discovery. In addition to enlarging sample size and providing a platform for replication studies, expanding consortia to international sites can enable studies of more ancestrally and geographically diverse populations.…”

Precision Medicine in Kidney Transplantation: Just Hype or a Realistic Hope?

“…Results from the International Genetics and Translational Research in Transplantation Network, a multisite consortium (n = 28 015) with adequate power to capture both rare and common genetic contributions to ESRD and posttransplant outcomes is expected soon. 150 …”

Early detection of SARS‐CoV‐2 and other infections in solid organ transplant recipients and household members using wearable devices

“…Such approaches are anticipated to save time for the clinical care team by decreasing the amount of data they need to examine and they may only need to consult via telemedicine with the patients/parents whose smartwatches trigger a sustained high confidence alert. Additional recruitments of heart, liver, and lung pediatric transplant recipients are also underway through sites in the International Genetics & Translational Research in Transplantation Network (iGeneTRAiN) [43,44], and details and resource related to the wearable studies are continuously updated 56.…”