{"doi":"10.1016/j.ebiom.2023.104838","title":"Clinical consequences of a genetic predisposition toward higher benign prostate-specific antigen levels","abstract":"BACKGROUND: Prostate-specific antigen (PSA) levels are influenced by genetic variation unrelated to prostate cancer risk. Whether a genetic predisposition to a higher PSA level predisposes to a diagnostic work-up for prostate cancer is not known. METHODS: Participants were 3110 men of African and European ancestries ages 45-70, without prostate cancer and with a baseline PSA < 4 ng/mL, undergoing routine clinical PSA screening. The exposure was a polygenic score (PGS) comprising 111 single nucleotide polymorphisms associated with PSA level, but not prostate cancer. We tested whether the PGS was associated with a: 1) PSA value > 4 ng/mL, 2) International Classification of Diseases (ICD) code for an elevated PSA, 3) encounter with a urologist, or 4) prostate biopsy. Multivariable Cox proportional hazards models were adjusted for age and genetic principal components. Analyses were stratified by age (45-59 years, and 60-70 years old). Association estimates are per standard deviation change in the PGS. FINDINGS: ), and undergoing a prostate biopsy (HR = 1.35 [1.11-1.64], p = 0.002). Among men ages 60-70, association effect sizes were smaller and not significant. INTERPRETATION: A predisposition toward higher PSA levels was associated with clinical evaluations of an elevated PSA among men ages 45-59 years. FUNDING: National Institutes of Health (NIH).","journal":"EBioMedicine","year":2023,"id":386903,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"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":1023777,"name":"John P. Shelley","orcid":"0000-0002-8612-3022","position":1,"is_corresponding":false},{"id":744818,"name":"Kerry Schaffer","orcid":"0000-0002-0097-1574","position":2,"is_corresponding":false},{"id":467316,"name":"Jeffrey J. Tosoian","orcid":"0000-0002-7614-9931","position":3,"is_corresponding":false},{"id":484412,"name":"Minoo Bagheri","orcid":"0000-0002-6093-613X","position":4,"is_corresponding":false},{"id":233930,"name":"John S. Witte","orcid":"0000-0003-0146-1434","position":5,"is_corresponding":false},{"id":233918,"name":"Linda Kachuri","orcid":"0000-0002-3226-4727","position":6,"is_corresponding":false},{"id":405424,"name":"Jonathan D. Mosley","orcid":"0000-0001-6421-2887","position":7,"is_corresponding":false},{"id":405425,"name":"Mingjian Shi","orcid":"0000-0003-1569-9822","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-19T01:18:00.717763Z","pmid":"37865044","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":[]}