PMID- 33655195
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240331
IS  - 2515-4826 (Electronic)
IS  - 2515-4826 (Linking)
VI  - 3
DP  - 2020
TI  - The relationship between donor-recipient genetic distance and long-term kidney 
      transplant outcome.
PG  - 47
LID - 10.12688/hrbopenres.13021.1 [doi]
LID - 47
AB  - 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).
CI  - Copyright: (c) 2020 Stapleton CP et al.
FAU - Stapleton, Caragh P
AU  - Stapleton CP
AUID- ORCID: 0000-0002-5354-7822
AD  - Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in 
      Ireland, Dublin, Ireland.
FAU - Lord, Graham M
AU  - Lord GM
AUID- ORCID: 0000-0003-2069-4743
AD  - Faculty of Biology, Medicine and Health, University of Manchester, Manchester, 
      UK.
AD  - NIHR Biomedical Research Centre at Guy's and St Thomas', NHS Foundation Trust and 
      King's College London, London, UK.
CN  - UK and Ireland Renal Transplant Consortium
FAU - Conlon, Peter J
AU  - Conlon PJ
AD  - Department of Nephrology, Beaumont Hospital, Dublin, Dublin, Ireland.
AD  - Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
FAU - Cavalleri, Gianpiero L
AU  - Cavalleri GL
AUID- ORCID: 0000-0002-9802-0506
AD  - Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in 
      Ireland, Dublin, Ireland.
LA  - eng
GR  - G0802068/MRC_/Medical Research Council/United Kingdom
GR  - G0600698/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - MR/J006742/1/MRC_/Medical Research Council/United Kingdom
GR  - MR/K002996/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20200729
PL  - Ireland
TA  - HRB Open Res
JT  - HRB open research
JID - 101754913
PMC - PMC7888353
OTO - NOTNLM
OT  - HLA
OT  - graft failure
OT  - identity-by-descent
OT  - identity-by-state
OT  - kidney transplant
OT  - shared genetic ancestry
OT  - transplant
COIS- No competing interests were disclosed.
EDAT- 2021/03/04 06:00
MHDA- 2021/03/04 06:01
PMCR- 2020/07/29
CRDT- 2021/03/03 05:49
PHST- 2020/06/29 00:00 [accepted]
PHST- 2021/03/03 05:49 [entrez]
PHST- 2021/03/04 06:00 [pubmed]
PHST- 2021/03/04 06:01 [medline]
PHST- 2020/07/29 00:00 [pmc-release]
AID - 10.12688/hrbopenres.13021.1 [doi]
PST - epublish
SO  - HRB Open Res. 2020 Jul 29;3:47. doi: 10.12688/hrbopenres.13021.1. eCollection 
      2020.