Genome‐wide association study for time to failure of kidney transplants from African American deceased donors
- 25 April 2020
- journal article
- research article
- Published by Wiley in Clinical Transplantation
- Vol. 34 (6), e13827
- https://doi.org/10.1111/ctr.13827
Abstract
Two renal‐risk variants in the apolipoprotein L1 gene (APOL1) in African American (AA) deceased donors (DD) are associated with shorter renal allograft survival after transplantation. To identify additional genes contributing to allograft survival, a genome‐wide association study was performed in 532 AA DDs. Phenotypic data were obtained from the Scientific Registry of Transplant Recipients. Association and single nucleotide polymorphism (SNP)‐by‐APOL1 interaction tests were conducted using death‐censored renal allograft survival accounting for relevant covariates. Replication and inverse‐variance weighted meta‐analysis were performed using data from 250 AA DD in the Genomics of Transplantation study. Accounting for APOL1, multiple SNPs near the Nudix Hydrolase 7 gene (NUDT7) showed strong independent effects (p=1.6x10‐8‐2.2x10‐8). Several SNPs in the Translocation protein SEC63 homolog (SEC63; p=2x10‐9‐3.7x10‐8) and plasmacytoma variant translocation 1 (PVT1) genes (p=4.0x10‐8‐7x10‐8) modified the effect of APOL1 on allograft survival. SEC63 is expressed in human renal tubule cells and glomeruli and PVT1 is associated with diabetic kidney disease. Overall, associations were detected for 41 SNPs (p=2x10‐9‐5x10‐8) contributing independently or interacting with APOL1 to impact renal allograft survival after transplantation from AA DD. Given the small sample size of the discovery and replication sets, independent validations and functional genomic efforts are needed to validate these results.Keywords
Funding Information
- National Institute on Aging (AI070119, AI140303)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK070941)
- National Institute on Minority Health and Health Disparities (MD009055)
This publication has 59 references indexed in Scilit:
- Association of APOL1 variants with mild kidney disease in the first-degree relatives of African American patients with non-diabetic end-stage renal diseaseKidney International, 2012
- APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-Associated NephropathyJournal of the American Society of Nephrology, 2011
- Functional Characterization of the Plasmacytoma Variant Translocation 1 Gene (PVT1) in Diabetic NephropathyPLOS ONE, 2011
- The APOL1 Gene and Allograft Survival after Kidney TransplantationAmerican Journal of Transplantation, 2011
- Fast model-based estimation of ancestry in unrelated individualsGenome Research, 2009
- White/Black Racial Differences in Risk of End-stage Renal Disease and DeathThe American Journal of Medicine, 2009
- Rapid and Accurate Multiple Testing Correction and Power Estimation for Millions of Correlated MarkersPLoS Genetics, 2009
- Principal components analysis corrects for stratification in genome-wide association studiesNature Genetics, 2006
- The Robust Inference for the Cox Proportional Hazards ModelJournal of the American Statistical Association, 1989
- Longitudinal data analysis using generalized linear modelsBiometrika, 1986