{"doi":"10.7554/elife.88538.1","title":"Association between APOL1 risk variants and progression from infection to sepsis","abstract":"Abstract Importance Two risk variants in the apolipoprotein L1 gene (APOL1) have been associated with increased susceptibility to sepsis in Black patients. However, it remains unclear whether APOL1 high-risk genotypes are associated with either progression from infection to sepsis or sepsis-related phenotypes, independent of their association with severe renal disease. Objective To examine the association between APOL1 high-risk genotypes and the risk of progression from infection to sepsis and sepsis-related phenotypes. Design, setting, and participants A retrospective cohort study of 2,242 Black patients hospitalized with an infection. Exposures Carriage of APOL1 high-risk genotypes. Main outcomes and measures The primary outcome was sepsis; secondary outcomes were death and organ failure related to sepsis. Results Of 2,242 Black patients hospitalized with infections, 565 developed sepsis. Patients with high-risk APOL1 genotypes had a significantly increased risk of sepsis (odds ratio [OR]=1.29 [95% CI, 1.00–1.67; p=0.047]); however, this association was not significant after adjustment for pre-existing severe renal disease (OR=1.14 [95% CI, 0.88-1.48; p=0.33]), nor after exclusion of those patients with pre-existing severe renal disease (OR=0.99 [95% CI, 0.70-1.39; p=0.95]. APOL1 high-risk genotypes were significantly associated with the renal dysfunction component of the Sepsis-3 criteria (OR=1.64 [95% CI, 1.21–2.22; p=0.001], but not with other sepsis-related organ dysfunction or death. The association between high-risk APOL1 genotypes and sepsis-related renal dysfunction was markedly attenuated by adjusting for pre-existing severe renal disease (OR=1.36 [95% CI, 1.00–1.86; p=0.05]) and was nullified after exclusion of patients with pre-existing severe renal disease (OR=1.16 [95% CI, 0.74–1.81; p=0.52]). Conclusion and relevance APOL1 high-risk genotypes were associated with an increased risk of sepsis; however, this increased risk was attributable predominantly to pre-existing renal disease.","journal":null,"year":2023,"id":409082,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":141085,"name":"Ge Liu","orcid":null,"position":1,"is_corresponding":false},{"id":956295,"name":"Annette Oeser","orcid":null,"position":2,"is_corresponding":false},{"id":493531,"name":"Andrea Ihegword","orcid":"0000-0002-2059-0824","position":3,"is_corresponding":false},{"id":422422,"name":"Alyson L. Dickson","orcid":"0000-0003-3404-3802","position":4,"is_corresponding":false},{"id":580234,"name":"Laura L. Daniel","orcid":"0000-0003-3143-5915","position":5,"is_corresponding":false},{"id":11400,"name":"Adriana M. Hung","orcid":"0000-0002-3203-1608","position":6,"is_corresponding":false},{"id":103608,"name":"Nancy J. Cox","orcid":"0000-0001-9315-0830","position":7,"is_corresponding":false},{"id":273407,"name":"Cecilia P. Chung","orcid":"0000-0001-5908-9423","position":8,"is_corresponding":false},{"id":58249,"name":"Wei‐Qi Wei","orcid":null,"position":9,"is_corresponding":false},{"id":367910,"name":"C. Michael Stein","orcid":null,"position":10,"is_corresponding":false},{"id":58243,"name":"Qiping Feng","orcid":"0000-0002-6213-793X","position":11,"is_corresponding":false},{"id":253975,"name":"Lan Jiang","orcid":"0000-0002-2583-3661","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:21:22.368387Z","pmid":null,"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":[]}