1. The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population.
- Author
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Stapleton CP, Heinzel A, Guan W, van der Most PJ, van Setten J, Lord GM, Keating BJ, Israni AK, de Borst MH, Bakker SJL, Snieder H, Weale ME, Delaney F, Hernandez-Fuentes MP, Reindl-Schwaighofer R, Oberbauer R, Jacobson PA, Mark PB, Chapman FA, Phelan PJ, Kennedy C, Sexton D, Murray S, Jardine A, Traynor JP, McKnight AJ, Maxwell AP, Smyth LJ, Oetting WS, Matas AJ, Mannon RB, Schladt DP, Iklé DN, Cavalleri GL, and Conlon PJ
- Subjects
- Adult, Europe epidemiology, Female, Follow-Up Studies, Genome-Wide Association Study, Glomerular Filtration Rate, Graft Rejection epidemiology, Graft Rejection genetics, Graft Survival, Humans, Kidney Failure, Chronic genetics, Kidney Failure, Chronic surgery, Kidney Function Tests, Living Donors statistics & numerical data, Male, Middle Aged, Postoperative Complications epidemiology, Postoperative Complications genetics, Prognosis, Retrospective Studies, Risk Factors, Transplant Recipients statistics & numerical data, Genetic Markers, Genetic Variation, Graft Rejection diagnosis, Kidney physiopathology, Kidney Transplantation adverse effects, Postoperative Complications diagnosis, Risk Assessment methods
- 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., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2019
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