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.
Highlights
The global prevalence of end-stage renal disease (ESRD) continues to climb
Genome-wide association studies (GWAS) among patients with chronic kidney disease (CKD) have detected both rare and common genetic variants significantly associated with estimated glomerular filtration rate decline and microalbuminuria, some of the strongest predictors of CKD outcomes, despite >80% of GWAS participants having eGFRs in the normal range (Boger et al, 2011a; Boger et al, 2011b;Reznichenko et al, 2012; Gorski et al, 2015; Parsa et al, 2017; Limou et al, 2018)
We are working to increase our understanding of the genetic underpinnings of ESRD and primary disease through single nucleotide polymorphism (SNP) based GWAS, copy number variant (CNV) screening, donor-recipient properties, allogenicity, and transplant outcomes
Summary
The global prevalence of end-stage renal disease (ESRD) continues to climb. In 2016, 19,301 kidney transplants were performed in the United States, and approximately five times as many were performed worldwide. We obtained formal clinical diagnoses of primary cause of ESRD, organized into disease categories of diabetic, arteriopathic, glomerular, acute kidney injury, infective and obstructive nephropathy, congenital, familial, toxic nephropathy, and malignancies, for all iGeneTRAiN kidney cohort subjects (Table 1) With these datasets, we are working to increase our understanding of the genetic underpinnings of ESRD and primary disease through single nucleotide polymorphism (SNP) based GWAS, copy number variant (CNV) screening, donor-recipient properties, allogenicity, and transplant outcomes. A major advantage of the newer software is the ability to detect duplications as well as 0, 1, and 2 copy deletions (Figure 2)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
