., International Genetics and Translational Research in Transplantation Network

., UK and Ireland Renal Transplant Consortium

McKnight, Amy

Stapleton, Caragh

BackgroundPrevious 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.MethodsWe 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.ResultsNo 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.ConclusionNo 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.AuthorsStapleton, Caragh P., Royal College of Surgeons, Dublin, IrelandPhelan, Paul J., Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, United KingdomChapman, Fiona A, NHS Scotland, Glasgow, United KingdomMaxwell, Alexander P., Queen's University Belfast, Belfast, United KingdomMcKnight, A.J., Queen's University Belfast, Belfast, United KingdomSexton, Donal J., The Irish Longitudinal Study on Ageing (TILDA), Trinity College Dublin., Dublin, IrelandBirdwell, Kelly A., Vanderbilt University, Nashville, Tennessee, United StatesKeating, Brendan, University of Pennsylvania, Philadelphia, Pennsylvania, United StatesCavalleri, Gianpiero, Royal College of Surgeons, Dublin, IrelandConlon, Peter J., Beaumont Hospital, Dublin 9, Co Dublin, IrelandLord, Graham M., King's College London, London, United KingdomDe Borst, Martin H., University Medical Center Groningen, Groningen, NetherlandsSnieder, Harold, University Medical Center Groningen, Groningen, NetherlandsKennedy, Claire, Beaumont Hospital, Dublin 9, Co Dublin, IrelandHernandez-Fuentes, Maria P., King's College London, London, United KingdomWeale, Michael, King's College London, London, United KingdomDelaney, Florence R., Guy's and St Thomas' NHS Foundation Trust, London, United KingdomMark, Patrick B., University of Glasgow, Glasgow, United KingdomGroup or Team NameUK and Ireland Renal Transplant Consortium; International Genetics and Translational Research in Transplantation Networ

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

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