Abstract: FR-PO1050

A Donor and Recipient Genome-Wide Association Study of Renal Allograft Function

Session Information

Category: Transplantation

  • 1702 Transplantation: Clinical and Translational

Authors

  • Stapleton, Caragh P., Royal College of Surgeons, Dublin, Ireland
  • Phelan, Paul J., Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, United Kingdom
  • Chapman, Fiona A, NHS Scotland, Glasgow, United Kingdom
  • Maxwell, Alexander P., Queen's University Belfast, Belfast, United Kingdom
  • McKnight, A.J., Queen's University Belfast, Belfast, United Kingdom
  • Sexton, Donal J., The Irish Longitudinal Study on Ageing (TILDA), Trinity College Dublin., Dublin, Ireland
  • Birdwell, Kelly A., Vanderbilt University, Nashville, Tennessee, United States
  • Keating, Brendan, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Cavalleri, Gianpiero, Royal College of Surgeons, Dublin, Ireland
  • Conlon, Peter J., Beaumont Hospital, Dublin 9, Co Dublin, Ireland
  • Lord, Graham M., King's College London, London, United Kingdom
  • De Borst, Martin H., University Medical Center Groningen, Groningen, Netherlands
  • Snieder, Harold, University Medical Center Groningen, Groningen, Netherlands
  • Kennedy, Claire, Beaumont Hospital, Dublin 9, Co Dublin, Ireland
  • Hernandez-Fuentes, Maria P., King's College London, London, United Kingdom
  • Weale, Michael, King's College London, London, United Kingdom
  • Delaney, Florence R., Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
  • Mark, Patrick B., University of Glasgow, Glasgow, United Kingdom

Group or Team Name

  • UK and Ireland Renal Transplant Consortium; International Genetics and Translational Research in Transplantation Network
Background

Previous studies have suggested the influence of common genetic variation on renal transplant outcome. Our aim was to expand on these studies and examine single variant effects of both donor and recipient genotypes on graft function (using estimated glomerular filtration rate (eGFR) as a proxy) taking a genome-wide association study (GWAS) approach.

Methods

We meta-analysed donor and recipient genetic variants across two cohorts (Netherlands cohort and UK/Ireland cohort). We carried out both donor and recipient GWAS of eGFR at 1 year (n donors=2,344; n recipients=2,840) and 5 years (n donors=2,190; n recipients=2,606) post-kidney transplant and examined change in eGFR between 1 and 5 years (Δ eGFR; n donors=1,678; n recipients=2,002). For the 1 year and 5 year analysis, where eGFR was missing due to death/failure the last known eGFR was used and death/failure was included as a covariate in the analysis. Samples with death/failure before 5 years were excluded in the Δ eGFR GWAS. Other covariates included the first eight principle components, donor and recipient age, donor type (living/deceased) and donor gender.

Results

No genome-wide significant associations were found in the three donor GWAS. In the recipient 5 year eGFR GWAS a significant association was observed with a locus on chromosome 19 (combined p=2.59x10-8). The presence of the minor allele correlated with a decrease in eGFR (beta= -0.15). This region contains the gene ZSCAN18 which may play a role in transcriptional regulation.

Conclusion

No single common genetic variant was associated with 1 year, 5 year or Δ eGFR in the donor GWAS. We detected a locus on chromosome 19 that associated with 5 year eGFR in the recipient GWAS suggesting that recipient genotype may be used to predict medium-term renal allograft outcome. Further work is required to assess the robustness of this signal and to replicate these findings.

Funding

  • Government Support - Non-U.S.