The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population
Year: 2019
Type: article
Study design: Observational Study
Abstract: Genetic variation across the human leukocyte antigen loci is known to influence renal-transplant outcome. However, the impact of genetic variation beyond the human leukocyte antigen loci is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with posttransplant eGFR at different time-points, out to 5 years posttransplantation. We conducted GWAS meta-analyses across 10 844 donors and recipients from five European ancestry cohorts. We also analyzed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with nontransplant eGFR, on posttransplant eGFR. PRS calculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFR at 1-year posttransplant. Thirty-two percent of the variability in eGFR at 1-year posttransplant was explained by our model containing clinical covariates (including weights for death/graft-failure), principal components and combined donor-recipient PRS, with 0.3% contributed by the PRS. No individual genetic variant was significantly associated with eGFR posttransplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a posttransplant context. Despite PRS being a significant predictor of eGFR posttransplant, the effect size of common genetic factors is limited compared to clinical variables.
DOI: 10.1111/ajt.15326
Authors: Caragh P. Stapleton, Andreas Heinzel, Weihua Guan, Peter J. van der Most, Jessica van Setten, Graham M. Lord, Brendan J. Keating, Ajay K. Israni, Martin H. de Borst, Stephan J.L. Bakker, Harold Snieder, Michael E. Weale, Florence Delaney, Maria P. Hernandez-Fuentes, Roman Reindl-Schwaighofer, Rainer Oberbauer, Pamala A. Jacobson, Patrick B. Mark, Fiona A. Chapman, Paul J. Phelan, Claire Kennedy, Donal Sexton, Susan Murray, Alan Jardine, Jamie P. Traynor, Amy Jayne McKnight, Alexander P. Maxwell, Laura J. Smyth, William S. Oetting, Arthur J. Matas, Roslyn B. Mannon, David P. Schladt, David N. Iklé, Gianpiero L. Cavalleri, Peter J. Conlon
Institutions: Royal College of Surgeons in Ireland, Medical University of Vienna, University of Minnesota, University Medical Center Groningen, University of Groningen, Utrecht University, University Medical Center Utrecht, King's College London, Guy's and St Thomas' NHS Foundation Trust, University of Manchester, University of Pennsylvania, Hennepin County Medical Center, University of Glasgow, NHS Lothian, Edinburgh Royal Infirmary, Beaumont Hospital, Queen's University Belfast, University of Alabama at Birmingham, Hennepin Healthcare Research Institute, Rho (United States)
Language: English
Subfield: Transplantation
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,300
Awards: G1222662094, Discovery of an integrated risk profile for chronic kidney disease and development of a clinical biomarker panel for personalising medicine, G1753726667, G1994517682, G2207605493, G2311296441, G277117613, G3923856125, G4432921003, G5144943808, G6071898252, G6247579670, G7533620376, Identifying biomarkers and mechanistic pathways to improve organ utilisation and kidney transplant outcomes
OpenAlex ID: W2916103308