The relationship between donor-recipient genetic distance and long-term kidney transplant outcome [version 1; peer review: 3 approved]
Background: We set out to quantify shared genetic ancestry between unrelated kidney donor-recipient pairs and test it as a predictor of time to graft failure.
Methods: In a homogenous, unrelated, European cohort of deceased-donor kidney transplant pairs (n pairs = 1,808), we calculated, using common genetic variation, shared ancestry at the genic (n loci=40,053) and genomic level. We conducted a sub-analysis focused on transmembrane protein coding genes (n transcripts=8,637) and attempted replication of a previously published nonsynonymous transmembrane mismatch score. Measures of shared genetic ancestry were tested in a survival model against time to death-censored graft failure
Results: Shared ancestry calculated across the human leukocyte antigen (HLA) significantly associated with graft survival in individuals who had a high serological mismatch (n pairs = 186) with those who did not have any HLA mismatches indicating that shared ancestry calculated specific loci can capture known associations with genes impacting graft outcome. None of the other measures of shared ancestry at a genic level, genome-wide scale, transmembrane subset or nonsynonymous transmembrane mismatch score analysis were significant predictors of time to graft failure.
Conclusions: In a large unrelated, deceased-donor European ancestry renal transplant cohort, shared donor-recipient genetic ancestry, calculated using common genetic variation, has limited value in predicting transplant outcome both on a genomic scale and at a genic level (other than at the HLA loci).
Irish Research Council and Punchestown Kidney Research Fund (grant number EPSPG2015)
Wellcome Trust (090355/A/09/Z, 090355/B/09/Z and 088849/Z/09/Z, “WTCCC3”)
Medical Research Council (grants G0600698 and MR/J006742/1; G0802068, G0801537/ID: 88245, MR/K002996/1)
Guy's and St Thomas’ Charity (grants R080530 and R090782)
European Union FP7 (grant agreement no HEALTH‐F5–2010–260687 and project number 305147: BIO‐DrIM)
National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas’ and King's College London
Wellcome Trust (Grant Codes WT098051 and WT091310),
National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Donor Health and Genomics at the University of Cambridge in partnership with NHS Blood and Transplant (NHSBT)
EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH‐F5‐2011‐282510)
CommentsThe original article and an updated version may be available on https://hrbopenresearch.org/
Published CitationStapleton CP, Lord GM; UK and Ireland Renal Transplant Consortium; Conlon PJ, Cavalleri GL. The relationship between donor-recipient genetic distance and long-term kidney transplant outcome [version 1; peer review: 3 approved]. HRB Open Res. 2020;3:47.
Publication Date29 July 2020
- Beaumont Hospital
- School of Pharmacy and Biomolecular Sciences
- Neurological and Psychiatric Disorders
PublisherF1000 Research Ltd