{"doi":"10.1038/s41598-024-71714-7","title":"A protein risk score for all-cause and respiratory-specific mortality in non-Hispanic white and African American individuals who smoke","abstract":"Protein biomarkers are associated with mortality in cardiovascular disease, but their effect on predicting respiratory and all-cause mortality is not clear. We tested whether a protein risk score (protRS) can improve prediction of all-cause mortality over clinical risk factors in smokers. We utilized smoking-enriched (COPDGene, LSC, SPIROMICS) and general population-based (MESA) cohorts with SomaScan proteomic and mortality data. We split COPDGene into training and testing sets (50:50) and developed a protRS based on respiratory mortality effect size and parsimony. We tested multivariable associations of the protRS with all-cause, respiratory, and cardiovascular mortality, and performed meta-analysis, area-under-the-curve (AUC), and network analyses. We included 2232 participants. In COPDGene, a penalized regression-based protRS was most highly associated with respiratory mortality (OR 9.2) and parsimonious (15 proteins). This protRS was associated with all-cause mortality (random effects HR 1.79 [95% CI 1.31-2.43]). Adding the protRS to clinical covariates improved all-cause mortality prediction in COPDGene (AUC 0.87 vs 0.82) and SPIROMICS (0.74 vs 0.6), but not in LSC and MESA. Protein-protein interaction network analyses implicate cytokine signaling, innate immune responses, and extracellular matrix turnover. A blood-based protein risk score predicts all-cause and respiratory mortality, identifies potential drivers of mortality, and demonstrates heterogeneity in effects amongst cohorts.","journal":"Scientific Reports","year":2024,"id":502855,"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":0.9527,"is_data_producer":false,"deposit_databanks":null,"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":578307,"name":"Katherine Pratte","orcid":"0000-0003-3358-8907","position":1,"is_corresponding":false},{"id":1027402,"name":"Catherine L. Debban","orcid":null,"position":2,"is_corresponding":false},{"id":939484,"name":"Congjian Liu","orcid":null,"position":3,"is_corresponding":false},{"id":361361,"name":"Steven A. Belinsky","orcid":"0000-0002-1240-2504","position":4,"is_corresponding":false},{"id":361360,"name":"Maria A. Picchi","orcid":"0000-0003-1067-0916","position":5,"is_corresponding":false},{"id":11381,"name":"Iain R. Konigsberg","orcid":"0000-0001-7356-100X","position":6,"is_corresponding":false},{"id":642258,"name":"Courtney Tern","orcid":"0000-0001-5029-595X","position":7,"is_corresponding":false},{"id":1352897,"name":"Heena Rijhwani","orcid":null,"position":8,"is_corresponding":false},{"id":267144,"name":"Brian D. Hobbs","orcid":"0000-0001-9564-0745","position":9,"is_corresponding":false},{"id":25018,"name":"Edwin K. Silverman","orcid":"0000-0002-3641-3822","position":10,"is_corresponding":false},{"id":305925,"name":"Yohannes Tesfaigzi","orcid":"0000-0002-3997-5839","position":11,"is_corresponding":false},{"id":11274,"name":"Stephen S. Rich","orcid":"0000-0003-3872-7793","position":12,"is_corresponding":false},{"id":11275,"name":"Ani Manichaikul","orcid":"0000-0002-5998-795X","position":13,"is_corresponding":false},{"id":11276,"name":"Jerome I. Rotter","orcid":"0000-0001-7191-1723","position":14,"is_corresponding":false},{"id":725285,"name":"Russel P. Bowler","orcid":null,"position":15,"is_corresponding":false},{"id":91951,"name":"Michael H. Cho","orcid":null,"position":16,"is_corresponding":false},{"id":267133,"name":"Matthew Moll","orcid":"0000-0002-0683-0975","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:10:27.781502Z","pmid":"39232179","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":[]}