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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.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    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.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    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).\n                  <\/ns4:p>","DOI":"10.12688\/hrbopenres.13021.1","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T05:05:07Z","timestamp":1595999107000},"page":"47","update-policy":"https:\/\/doi.org\/10.12688\/hrbopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["The relationship between donor-recipient genetic distance and long-term kidney transplant outcome"],"prefix":"10.12688","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5354-7822","authenticated-orcid":false,"given":"Caragh P.","family":"Stapleton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2069-4743","authenticated-orcid":false,"given":"Graham M.","family":"Lord","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"UK and Ireland Renal Transplant Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Conlon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9802-0506","authenticated-orcid":false,"given":"Gianpiero L.","family":"Cavalleri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2020,7,29]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"385-387","DOI":"10.1159\/000465134","article-title":"Report on the Workshop on Histocompatibility Testing, held in Leiden, August 1965.","volume":"11","year":"1966","journal-title":"Vox Sang."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"101-116","DOI":"10.1111\/j.1399-0039.2009.01291.x","article-title":"A short history of HLA.","volume":"74","author":"E Thorsby","year":"2009","journal-title":"Tissue antigens."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"1501-1508","DOI":"10.1111\/j.1600-6143.2004.00535.x","article-title":"Diminishing significance of HLA matching in kidney transplantation.","volume":"4","author":"X Su","year":"2004","journal-title":"Am J 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Registry.","volume":"67","author":"L Tjaden","year":"2016","journal-title":"Am J Kidney Dis."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"e0195038","DOI":"10.1371\/journal.pone.0195038","article-title":"Ethnicity matching and outcomes after kidney transplantation in the United Kingdom.","volume":"13","author":"B Pisavadia","year":"2018","journal-title":"PLoS One."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"e1005088","DOI":"10.1371\/journal.pcbi.1005088","article-title":"Exome Sequencing and Prediction of Long-Term Kidney Allograft Function.","volume":"12","author":"L Mesnard","year":"2016","journal-title":"PLoS Comput Biol."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"910-917","DOI":"10.1016\/S0140-6736(18)32473-5","article-title":"Contribution of non-HLA incompatibility between donor and recipient to kidney allograft survival: genome-wide analysis in a prospective cohort.","volume":"393","author":"R Reindl-Schwaighofer","year":"2019","journal-title":"Lancet."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"e1002453","DOI":"10.1371\/journal.pgen.1002453","article-title":"Inference of population structure using dense haplotype data.","volume":"8","author":"D Lawson","year":"2012","journal-title":"PLoS Genet."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"1370-1379","DOI":"10.1111\/ajt.14594","article-title":"Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study.","volume":"18","author":"M Hernandez-Fuentes","year":"2018","journal-title":"Am J Transplant."},{"key":"ref-12","article-title":"Supplementary Information: The relationship between donor-recipient genetic distance and long-term kidney transplant outcome","author":"C Stapleton","year":"2020"},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets.","volume":"4","author":"C Chang","year":"2015","journal-title":"GigaScience."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"559-575","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses.","volume":"81","author":"S Purcell","year":"2007","journal-title":"Am J Hum Genet."},{"key":"ref-15","article-title":"A Package for Survival Analysis in S","author":"T Therneau","year":"2015"},{"key":"ref-16","article-title":"R: A language and environment for statistical computing","year":"2017"},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"996-1006","DOI":"10.1101\/gr.229102","article-title":"The human genome browser at UCSC.","volume":"12","author":"W Kent","year":"2002","journal-title":"Genome Res."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"1521-1531","DOI":"10.1534\/genetics.111.136937","article-title":"Detecting rare 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/hrbopenres.14114.r27907, Adrian Dockery, The School of Genetics & Microbiology, Trinity College Dublin, Dublin, Ireland, 10 Sep 2020, version 1, indexed","URL":"https:\/\/hrbopenresearch.org\/articles\/3-47\/v1#referee-response-27907","order":0,"name":"referee-response-27907","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/hrbopenres.14114.r28649, Krzysztof Kiryluk, Department of Medicine, Division of Nephrology, Columbia University, College of Physicians & Surgeons, New York, New York, USA, 16 Feb 2021, version 1, indexed","URL":"https:\/\/hrbopenresearch.org\/articles\/3-47\/v1#referee-response-28649","order":1,"name":"referee-response-28649","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"C.P.S is supported by the Irish Research Council and Punchestown Kidney Research Fund (grant number EPSPG2015). Supported by grants awarded from the Wellcome Trust (090355\/A\/09\/Z, 090355\/B\/09\/Z and 088849\/Z\/09\/Z, \u201cWTCCC3\u201d), the Medical Research Council (grants G0600698 and MR\/J006742\/1 to S.H.S.; G0802068, G0801537\/ID: 88245 to G.M.L. and MR\/K002996\/1 to G.M.L; grants G0801537\/ID: 88245), Guy's and St Thomas\u2019 Charity (grants R080530 and R090782) to M.H.F. and G.M.L., from the European Union FP7 (grant agreement no HEALTH\u2010F5\u20132010\u2013260687 to M.H.F. and project number 305147: BIO\u2010DrIM to M.H.F. and I.R.M.); and by the National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas\u2019 and King's College London. Anonymized clinical data were also provided NIHR Health Informatics Collaborative. N.S.'s research is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH\u2010F5\u20102011\u2010282510) and the 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). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health, or NHSBT. The NIHR Health Informatics Collaborative includes Bradley JR, University of Cambridge; Channon KM, University of Oxford; Lord GM, King's College London; Weber J, Imperial College London; Williams B, University College London; Crichton C, University of Oxford; Davies J, University of Oxford; Welch J, University of Oxford; and Woods K, Oxford University Hospitals NHS Foundation Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}