{"doi":"10.1371/journal.pone.0303446","title":"Polygenic risk score for acute rejection based on donor-recipient non-HLA genotype mismatch","abstract":"BACKGROUND: Acute rejection (AR) after kidney transplantation is an important allograft complication. To reduce the risk of post-transplant AR, determination of kidney transplant donor-recipient mismatching focuses on blood type and human leukocyte antigens (HLA), while it remains unclear whether non-HLA genetic mismatching is related to post-transplant complications. METHODS: We carried out a genome-wide scan (HLA and non-HLA regions) on AR with a large kidney transplant cohort of 784 living donor-recipient pairs of European ancestry. An AR polygenic risk score (PRS) was constructed with the non-HLA single nucleotide polymorphisms (SNPs) filtered by independence (r2 < 0.2) and P-value (< 1×10-3) criteria. The PRS was validated in an independent cohort of 352 living donor-recipient pairs. RESULTS: By the genome-wide scan, we identified one significant SNP rs6749137 with HR = 2.49 and P-value = 2.15×10-8. 1,307 non-HLA PRS SNPs passed the clumping plus thresholding and the PRS exhibited significant association with the AR in the validation cohort (HR = 1.54, 95% CI = (1.07, 2.22), p = 0.019). Further pathway analysis attributed the PRS genes into 13 categories, and the over-representation test identified 42 significant biological processes, the most significant of which is the cell morphogenesis (GO:0000902), with 4.08 fold of the percentage from homo species reference and FDR-adjusted P-value = 8.6×10-4. CONCLUSIONS: Our results show the importance of donor-recipient mismatching in non-HLA regions. Additional work will be needed to understand the role of SNPs included in the PRS and to further improve donor-recipient genetic matching algorithms. Trial registry: Deterioration of Kidney Allograft Function Genomics (NCT00270712) and Genomics of Kidney Transplantation (NCT01714440) are registered on ClinicalTrials.gov.","journal":"PLoS ONE","year":2024,"id":455945,"datarank":0.34092031553081853,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.049033793172521475,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.049033793172521475,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":6,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01714440"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":433911,"name":"David P. Schladt","orcid":"0000-0002-3793-5745","position":1,"is_corresponding":false},{"id":433915,"name":"Casey R. Dorr","orcid":"0000-0002-6108-280X","position":2,"is_corresponding":false},{"id":433916,"name":"Arthur J. Matas","orcid":"0000-0001-9957-639X","position":3,"is_corresponding":false},{"id":433918,"name":"William S. Oetting","orcid":"0000-0002-1076-0711","position":4,"is_corresponding":false},{"id":302262,"name":"Pamala A. Jacobson","orcid":"0000-0002-4145-7045","position":5,"is_corresponding":false},{"id":433917,"name":"Ajay K. Israni","orcid":"0000-0002-7607-0430","position":6,"is_corresponding":false},{"id":284712,"name":"Jinbo Chen","orcid":"0000-0003-3174-2552","position":7,"is_corresponding":false},{"id":334853,"name":"Weihua Guan","orcid":"0000-0002-0956-9821","position":8,"is_corresponding":false},{"id":912459,"name":"Rui Cao","orcid":"0009-0005-5157-2396","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T02:03:22.974789Z","pmid":"38820342","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}