Sibling transplant pairs have better transplant outcomes than unrelated donor recipient (DR) pairs indicating that shared genetic ancestry between donors and recipients can aid in predicting transplant outcome. Genome-wide SNP arrays provide high resolution genotype data which can be used to infer shared genetic ancestry. We set out to evaluate a number of methods that detect and quantify shared ancestry, to see which could best predict allograft outcome, using estimated glomerular filtration rate (eGFR) as a proxy.

We tested three different methods for estimating shared genetic ancestry on deceased donor DR pairs of European ancestry who were GWAS genotyped as part of the UK and Ireland Renal Transplant Consortium and the Wellcome Trust Case Control Consortium 3. Method 1 calculated identity by descent (IBD) which was then used to estimate the degree of relationship. Method 2 calculated genetic distance using identity by state (IBS). IBS examines the number of shared alleles across the genome. Method 3 created a mosaic of an individual's genome from the haplotypes of all the other individuals in the dataset and the similarity of mosaic genomes in a given DR pair was used as a measure of shared ancestry. Linear regression was used to correlate these measures of shared ancestry against eGFR at 1 year (DR pairs, n=1,450) and 5 years (DR pairs, n=1,309) post-kidney transplant and change in eGFR between 1 and 5 years ([Delta] eGFR; DR pairs, n=982). For the 1 year and 5 year analysis, where eGFR was missing due to death/graft failure the last known eGFR was used and death/graft failure was included as a covariate in the analysis. Samples with death/graft failure before 5 years were excluded in the [Delta] eGFR analysis. Other covariates included donor and recipient age and donor gender.

We did not find a significant correlation between any of the three measures of shared ancestry in the European ancestry deceased-donor DR pairs and graft function. The genetic relationship between the vast majority of our donor-recipient pairs was distant, and not detectable via IBD. The effect size of shared ancestry (at the genomic level) on eGFR is limited, and not detectable in our analysis.

CITATION INFORMATION: Stapleton C., On behalf of the UK and Ireland Renal Transplant Consortium, Conlon P., Cavalleri G. Shared Genetic Ancestry as a Predictor of Medium Term Renal Transplant Outcome in Deceased Donor Transplants Am J Transplant. 2017;17 (suppl 3).

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