{"id":193271,"date":"2024-07-21T14:33:15","date_gmt":"2024-07-21T19:33:15","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2024\/07\/blood-protein-assessment-of-leading-incident-diseases-and-mortality-in-the-uk-biobank"},"modified":"2024-07-21T14:33:15","modified_gmt":"2024-07-21T19:33:15","slug":"blood-protein-assessment-of-leading-incident-diseases-and-mortality-in-the-uk-biobank","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2024\/07\/blood-protein-assessment-of-leading-incident-diseases-and-mortality-in-the-uk-biobank","title":{"rendered":"Blood protein assessment of leading incident diseases and mortality in the UK Biobank"},"content":{"rendered":"<p><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/blood-protein-assessment-of-leading-incident-diseases-and-mortality-in-the-uk-biobank2.jpg\"><\/a><\/p>\n<p>Identifying individuals who are at a high risk of age-related morbidities may aid in personalized medicine. Circulating proteins can discriminate disease cases from controls and delineate the risk of incident diagnoses<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Yao, C. et al. Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease. Nat. Commun. 9, 3268 (2018).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR1\" id=\"ref-link-section-d591664055e654\">1<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Ferkingstad, E. et al. Large-scale integration of the plasma proteome with genetics and disease. Nat. Genet. 53, 1712&ndash;1721 (2021).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR2\" id=\"ref-link-section-d591664055e654_1\">2<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Pietzner, M. et al. Mapping the proteo-genomic convergence of human diseases. Science 374, eabj1541 (2021).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR3\" id=\"ref-link-section-d591664055e654_2\">3<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Sun, B. B. et al. Genomic atlas of the human plasma proteome. Nature 558, 73&ndash;79 (2018).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR4\" id=\"ref-link-section-d591664055e654_3\">4<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Gudmundsdottir, V. et al. Circulating protein signatures and causal candidates for type 2 diabetes. Diabetes 69, 1843&ndash;1853 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR5\" id=\"ref-link-section-d591664055e654_4\">5<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Nurmohamed, N. S. et al. Targeted proteomics improves cardiovascular risk prediction in secondary prevention. Eur. Heart J. 43, 1569&ndash;1577 (2022).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR6\" id=\"ref-link-section-d591664055e654_5\">6<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Huth, C. et al. Protein markers and risk of type 2 diabetes and prediabetes: a targeted proteomics approach in the KORA F4\/FF4 study. Eur. J. Epidemiol. 34409&ndash;422 (2019).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR7\" id=\"ref-link-section-d591664055e654_6\">7<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 8\" title=\"LaFramboise, W. A. et al. Serum protein profiles predict coronary artery disease in symptomatic patients referred for coronary angiography. BMC Med. 10,157 (2012).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR8\" id=\"ref-link-section-d591664055e657\">8<\/a><\/sup>. While singular protein markers offer insight into the mediators of disease<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 5\" title=\"Gudmundsdottir, V. et al. Circulating protein signatures and causal candidates for type 2 diabetes. Diabetes 69, 1843&ndash;1853 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR5\" id=\"ref-link-section-d591664055e661\">5<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Georgakis, M. K. & Gill, D. Mendelian randomization studies in stroke: exploration of risk factors and drug targets with human genetic data. Stroke https:\/\/doi.org\/10.1161\/STROKEAHA.120.032617 (2021).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR9\" id=\"ref-link-section-d591664055e664\">9<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Ritchie, S. C. et al. Integrative analysis of the plasma proteome and polygenic risk of cardiometabolic diseases. Nat. Metab. 3, 1476&ndash;1483 (2021).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR10\" id=\"ref-link-section-d591664055e664_1\">10<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 11\" title=\"Sathyan, S. et al. Plasma proteomic profile of age, health span, and all-cause mortality in older adults. Aging Cell 19, e13250 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR11\" id=\"ref-link-section-d591664055e667\">11<\/a><\/sup>, simultaneously harnessing multiple proteins may improve clinical utility<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 12\" title=\"Borrebaeck, C. A. K. Precision diagnostics: moving towards protein biomarker signatures of clinical utility in cancer. Nat. Rev. Cancer 17199&ndash;204 (2017).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR12\" id=\"ref-link-section-d591664055e671\">12<\/a><\/sup>. Clinically available non-omics scores such as QRISK typically profile the 10-year onset risk of a disease<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 13\" title=\"Hippisley-Cox, J., Coupland, C. & Brindle, P. Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study. BMJ 357, j2099 (2017).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR13\" id=\"ref-link-section-d591664055e675\">13<\/a><\/sup>. Proteomic scores have recently been trained on diabetes, cardiovascular and lifestyle traits as outcomes in 16,894 individuals<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 14\" title=\"Williams, S. A. et al. Plasma protein patterns as comprehensive indicators of health. Nat. Med. 25, 1851&ndash;1857 (2019).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR14\" id=\"ref-link-section-d591664055e679\">14<\/a><\/sup>. Proteomic and metabolomic scores have also been developed for time-to-event outcomes, including all-cause mortality<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 6\" title=\"Nurmohamed, N. S. et al. Targeted proteomics improves cardiovascular risk prediction in secondary prevention. Eur. Heart J. 43, 1569&ndash;1577 (2022).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR6\" id=\"ref-link-section-d591664055e684\">6<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Deelen, J. et al. A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals. Nat. Commun. 10, 3346 (2019).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR15\" id=\"ref-link-section-d591664055e687\">15<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Ganz, P. et al. Development and validation of a protein-based risk score for cardiovascular outcomes among patients with stable coronary heart disease. JAMA 315, 2532&ndash;2541 (2016).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR16\" id=\"ref-link-section-d591664055e687_1\">16<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Wang, Z. et al. Metabolomic pattern predicts incident coronary heart disease. Arterioscler. Thromb. Vasc. Biol. 39, 1475&ndash;1482 (2019).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR17\" id=\"ref-link-section-d591664055e687_2\">17<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Machado-Fragua, M. D. et al. Circulating serum metabolites as predictors of dementia: a machine learning approach in a 21-year follow-up of the Whitehall II cohort study. BMC Med. 20,334 (2022).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR18\" id=\"ref-link-section-d591664055e687_3\">18<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Eiriksdottir, T. et al. Predicting the probability of death using proteomics. Commun. Biol. 4,758 (2021).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR19\" id=\"ref-link-section-d591664055e687_4\">19<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" title=\"Lind, L. et al. Large-scale plasma protein profiling of incident myocardial infarction, ischemic stroke, and heart failure. J. Am. Heart Assoc. 10, e023330 (2021).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR20\" id=\"ref-link-section-d591664055e687_5\">20<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 21\" title=\"Buergel, T. et al. Metabolomic profiles predict individual multidisease outcomes. Nat. Med. 28, 2309&ndash;2320 (2022).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR21\" id=\"ref-link-section-d591664055e690\">21<\/a><\/sup>.<\/p>\n<p>Here, we demonstrate how large-scale proteomic sampling can identify candidate protein targets and facilitate the prediction of leading age-related incident outcomes in mid to later life (see the study design summary in Extended Data Fig. <a data-track=\"click\" data-track-label=\"link\" data-track-action=\"figure anchor\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#Fig4\">1<\/a>). We used 1,468 Olink plasma protein measurements in 47,600 individuals (aged 40\u201370 years) available as part of the UK Biobank Pharma Proteomics Project (UKB-PPP)<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 22\" title=\"Sun, B. B. et al. Plasma proteomic associations with genetics and health in the UK Biobank. Nature 622329&ndash;338 (2023).\" href=\"https:\/\/www.nature.com\/articles\/s43587-024-00655-7#ref-CR22\" id=\"ref-link-section-d591664055e700\">22<\/a><\/sup>. Cox proportional hazards (PH) models were used to characterize associations between each protein and 24 incident outcomes, ascertained through electronic health data linkage. Next, the dataset was randomly split into training and testing subsets to train proteomic scores (ProteinScores) and assess their utility for modeling either the 5-or 10-year onset of the 19 incident outcomes that had a minimum of 150 cases available. We modeled ProteinScores alongside clinical biomarkers, polygenic risk scores (PRS) and metabolomics measures to investigate how these markers may be used to augment risk stratification.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Identifying individuals who are at a high risk of age-related morbidities may aid in personalized medicine. Circulating proteins can discriminate disease cases from controls and delineate the risk of incident diagnoses1,2,3,4,5,6,7,8. While singular protein markers offer insight into the mediators of disease5,9,10,11, simultaneously harnessing multiple proteins may improve clinical utility12. Clinically available non-omics scores such [\u2026]<\/p>\n","protected":false},"author":662,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,269],"tags":[],"class_list":["post-193271","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-life-extension"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/193271","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/662"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=193271"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/193271\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=193271"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=193271"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=193271"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}