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

The UK Ireland Renal Transplant Consortium, DeKAF Genomics and GEN03 Studies, The International Genetics and Translational Research in Transplantation Network

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalAmerican Journal of Transplantation
DOIs
StatePublished - Jan 1 2019

Fingerprint

Glomerular Filtration Rate
Transplants
Kidney
Population
Genome-Wide Association Study
HLA Antigens
Genotype
Meta-Analysis
Weights and Measures

Keywords

  • basic (laboratory) research/science
  • clinical research/practice
  • genetics
  • genomics
  • glomerular filtration rate (GFR)
  • kidney transplantation/nephrology
  • microarray/gene array
  • molecular biology: DNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

The UK Ireland Renal Transplant Consortium, DeKAF Genomics and GEN03 Studies, & The International Genetics and Translational Research in Transplantation Network (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. https://doi.org/10.1111/ajt.15326

The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population. / The UK Ireland Renal Transplant Consortium; DeKAF Genomics and GEN03 Studies; The International Genetics and Translational Research in Transplantation Network.

In: American Journal of Transplantation, 01.01.2019.

Research output: Contribution to journalArticle

The UK Ireland Renal Transplant Consortium, DeKAF Genomics and GEN03 Studies & The International Genetics and Translational Research in Transplantation Network 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. https://doi.org/10.1111/ajt.15326
The UK Ireland Renal Transplant Consortium, DeKAF Genomics and GEN03 Studies, The International Genetics and Translational Research in Transplantation Network. 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. 2019 Jan 1. https://doi.org/10.1111/ajt.15326
The UK Ireland Renal Transplant Consortium ; DeKAF Genomics and GEN03 Studies ; The International Genetics and Translational Research in Transplantation Network. / The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population. In: American Journal of Transplantation. 2019.
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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.",
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KW - molecular biology: DNA

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