{"doi":"10.1016/j.chstcc.2025.100150","title":"A Computable Electronic Health Record ARDS Classifier and the Association Between the MUC5B Promoter Polymorphism and ARDS in Critically Ill Adults","abstract":"Background Large population-based DNA biobanks linked to electronic health records (EHRs) may provide novel opportunities to identify genetic drivers of ARDS. Research Question Can a computerized algorithm identify ARDS in a large EHR biobank database, and can this be used to identify ARDS genetic risk factors? Study Design and Methods We developed a classifier algorithm to identify a diagnosis of ARDS as identified from the electronic health record (EHR-ARDS) using diagnostic billing codes, laboratory test results, and chest radiography report text. The classifier model performance was evaluated against investigator-adjudicated ARDS using standard classification metrics including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the Cohen κ value. After confirming acceptable classifier performance, we evaluated the association between EHR-ARDS and the MUC5B promoter polymorphism rs35705950 in 2 parallel genotyped cohorts: a prospective biomarker cohort of critically ill adults (Validating Acute Lung Injury Biomarkers for Diagnosis [VALID]) and a retrospective cohort from our institution's de-identified EHR biobank, BioVU. Results We included 2,795 patients from VALID and 9,025 hospitalized participants from BioVU. EHR-ARDS showed moderate agreement with investigator-adjudicated ARDS (VALID: sensitivity, 0.86; specificity, 0.70; PPV, 0.49; NPV, 0.93; and κ, 0.45; BioVU: sensitivity, 0.94; specificity, 0.81; PPV, 0.66; NPV, 0.97; and κ, 0.67). We observed a significant age-gene interaction effect for EHR-ARDS in VALID: among older patients, rs35705950 was associated with increased EHR-ARDS risk (OR, 1.37; 95% CI, 1.05-1.78; P = .019), whereas among younger patients, this association was absent (OR, 0.92; 95% CI, 0.70-1.21; P = .55). In BioVU, rs35705950 was associated with EHR-ARDS among all participants (OR, 1.20; 95% CI, 1.01-1.43; P = .043); however, this effect did not vary by age. Interpretation The MUC5B promoter polymorphism was associated with EHR-ARDS in 2 parallel cohorts of at-risk adults. An age-gene effect modification was observed in VALID, whereas BioVU identified a consistent association between MUC5B and EHR-ARDS regardless of age. Our study highlights the potential for EHR biobanks to enable precision medicine ARDS studies.","journal":"CHEST Critical Care","year":2025,"id":552051,"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":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":321372,"name":"J. Brennan McNeil","orcid":"0000-0002-9200-1881","position":1,"is_corresponding":false},{"id":347760,"name":"Neil S. Zheng","orcid":"0000-0001-8737-0773","position":2,"is_corresponding":false},{"id":251656,"name":"Diana Chang","orcid":"0000-0002-0832-7177","position":3,"is_corresponding":false},{"id":1010966,"name":"Carrie M. Rosenberger","orcid":"0000-0002-8189-8822","position":4,"is_corresponding":false},{"id":52015,"name":"Angela J. Rogers","orcid":"0000-0001-6969-6200","position":5,"is_corresponding":false},{"id":312491,"name":"Julie A. Bastarache","orcid":"0000-0003-0458-6507","position":6,"is_corresponding":false},{"id":58243,"name":"Qiping Feng","orcid":"0000-0002-6213-793X","position":7,"is_corresponding":false},{"id":1371898,"name":"Wei-Qi Wei","orcid":"0000-0003-4985-056X","position":8,"is_corresponding":false},{"id":244826,"name":"Lorraine B. Ware","orcid":"0000-0002-9429-4702","position":9,"is_corresponding":false},{"id":317417,"name":"V. Eric Kerchberger","orcid":"0000-0002-0342-1965","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:54:29.318076Z","pmid":"41640800","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":[]}