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

Caragh Stapleton, Amy McKnight, UK and Ireland Renal Transplant Consortium ., International Genetics and Translational Research in Transplantation Network .

Research output: Contribution to conferenceAbstract

Abstract

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.


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
Original languageEnglish
Pages676
Publication statusPublished - 01 Oct 2017
EventAmerican Society of Nephrology 2017 conference - New Orleans, United States
Duration: 01 Nov 201705 Nov 2017

Conference

ConferenceAmerican Society of Nephrology 2017 conference
Abbreviated titleASN
CountryUnited States
CityNew Orleans
Period01/11/201705/11/2017

Bibliographical note

Journal of the American Society of Nephrology - Oct 2017 issue

Keywords

  • kidney disease
  • SNP
  • GWAS

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    Stapleton, C., McKnight, A., ., UK. A. I. R. T. C., & ., I. G. A. T. R. I. T. N. (2017). A Donor and Recipient Genome-wide Association Study of Renal Allograft Function. 676. Abstract from American Society of Nephrology 2017 conference, New Orleans, United States. file:///C:/Users/ajmck/AppData/Local/Packages/Microsoft.MicrosoftEdge_8wekyb3d8bbwe/TempState/Downloads/KW17Abstracts%20(1).pdf