The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population

Stapleton, C. P. et al. (2019) The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population. American Journal of Transplantation, 19(8), pp. 2262-2273. (doi: 10.1111/ajt.15326)

Abstract

Genetic variation across the HLA is known to influence renal‐transplant outcome. However, the impact of genetic variation beyond the HLA is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with post‐transplant eGFR at different time‐points, out to 5‐years post‐transplantation. We conducted GWAS meta‐analyses across 10,844 donors and recipients from five European ancestry cohorts. We also analysed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with non‐transplant eGFR, on post‐transplant eGFR. PRS calculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFR at 1‐year post‐transplant. 32% of the variability in eGFR at 1‐year post‐transplant 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 post‐transplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a post‐transplant context. Despite PRS being a significant predictor of eGFR post‐transplant, the effect size of common genetic factors is limited compared to clinical variables.

• Item Type: Articles
• Additional Information: C.P.S is supported by the Irish Research Council and Punchestown Kidney Research Fund (grant number EPSPG2015). P.J.P. is supported by an NRS Career Research Fellowship. Further thanks to funding support from Northern Ireland Kidney Research Fund and SFI-DfE (15/IA/3152). TransplantLines is registered at ClinicalTrials.gov with Identifier NCT03272841.The DEKAF and GEN03 studies are supported by 5U19-AI070119 & 5U01-AI058013 from NIAID.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mark, Professor Patrick and Traynor, Dr Jamie and Jardine, Professor Alan
• Authors: Stapleton, C. P., Heinzel, A., Guan, W., van der Most, P. J., van Setten, J., Lord, G. M., Keating, B. J., Israni, A. K., de Borst, M. H., Bakker, S. J.L., Snieder, H., Weale, M. E., Delaney, F., Hernandez-Fuentes, M. P., Reindl-Schwaighofer, R., Oberbauer, R., Jacobson, P. A., Mark, P. B., Chapman, F. A., Phelan, P. J., Kennedy, C., Sexton, D., Murray, S., Jardine, A., Traynor, J. P., McKnight, A. J., Maxwell, A. P., Smyth, L. J., Oetting, W. S., Matas, A. J., Mannon, R. B., Schladt, D. P., Iklé, D. N., Cavalleri, G. L., and Conlon, P. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: American Journal of Transplantation
• Publisher: Wiley-Blackwell Publishing, Inc.
• ISSN: 1600-6135
• ISSN (Online): 1600-6143
• Published Online: 27 February 2019
• Copyright Holders: Copyright © 2019 The American Society of Transplantation
• First Published: First published in American Journal of Transplantation 19(8):2262-2273
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher