{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T11:43:46Z","timestamp":1786189426090,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,6]]},"group-title":"Cardiovascular Medicine","reference-count":88,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Proteomics holds great promise for identifying potentially druggable effectors of common diseases, yet its application at population-scale across diverse ancestries, remains challenging. Here, we developed genetic imputation models for 2,594 plasma proteins using proteomic and genetic data from 54,219 UK Biobank participants, validating their performance across multiple ancestry groups and in an independent cohort. Plasma proteomes were then imputed for over 640,000 participants in the UK Biobank and the\n                  <jats:italic>All of Us<\/jats:italic>\n                  Research Program. To assess its aetiological value at population-scale, a further proteome-wide association study of cardiovascular diseases was performed across six genetic ancestries. We identified \u223c9000 protein-disease associations across 89 cardiovascular conditions (PheCodes), the majority of which show consistent effects across ancestries and biobanks, with many comprising known targets of drugs either approved or under development. The associations reveal both shared and distinct proteomic signatures across cardiovascular conditions and defined clusters of distinct pathophysiology with shared underlying molecular pathways. Integration of data on tissue specificity and single-cell transcriptomics prioritised liver-derived proteins in circulation as candidate effectors of coronary artery disease, highlighting inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) as a putative effector. Using a liver-targeted CRISPR gene-editing platform, we show that\n                  <jats:italic>in vivo<\/jats:italic>\n                  disruption of ITIH4 reduces plasma cholesterol and pro-atherogenic lipid species in a preclinical model, consistent with a causal role in cardiovascular disease. Our study enables study of large-scale proteomics in diverse populations, provides a systematic map of protein associations of cardiovascular diseases, and demonstrates the utility of genetically imputed proteomes for target discovery and experimental validation. To facilitate proteomic analyses for the research community, the resultant models and association results have been made freely available through the OmicsPred platform.\n                <\/jats:p>","DOI":"10.64898\/2026.08.04.26359685","type":"posted-content","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T20:15:17Z","timestamp":1786047317000},"source":"Crossref","is-referenced-by-count":0,"title":["A proteome-wide association study of cardiovascular diseases in 640,000 participants of multiple ancestries"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7304-5045","authenticated-orcid":false,"given":"Yu","family":"Xu","sequence":"first","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Loesch","sequence":"additional","affiliation":[{"name":"Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2088-5240","authenticated-orcid":false,"given":"Henry J.","family":"Taylor","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Keating","sequence":"additional","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia"},{"name":"Molecular Metabolism & Ageing Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia"},{"name":"CRISPR Validation Platform, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8454-9548","authenticated-orcid":false,"given":"Scott C.","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6773-9182","authenticated-orcid":false,"given":"Xilin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam","family":"Tran","sequence":"additional","affiliation":[{"name":"Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-9595","authenticated-orcid":false,"given":"Carles","family":"Foguet","sequence":"additional","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saniya","family":"Khullar","sequence":"additional","affiliation":[{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK"},{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Yin","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Persyn","sequence":"additional","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasanga D.","family":"Manikpurage","sequence":"additional","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8776-6719","authenticated-orcid":false,"given":"Emmanuela","family":"Bonglack","sequence":"additional","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7743-5991","authenticated-orcid":false,"given":"Chief","family":"Ben-Eghan","sequence":"additional","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Gil","sequence":"additional","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK"},{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongte","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Roberts","sequence":"additional","affiliation":[{"name":"National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK"},{"name":"NHS Blood and Transplant-Oxford Centre, John Radcliffe Hospital and Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6347-2281","authenticated-orcid":false,"given":"Benjamin","family":"Sun","sequence":"additional","affiliation":[{"name":"Informatics and Predictive Sciences, Research, Bristol Myers Squibb, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Runz","sequence":"additional","affiliation":[{"name":"Translational Sciences, Research and Development, Biogen Inc., Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Wood","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK"},{"name":"National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele Di","family":"Angelantonio","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK"},{"name":"National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Whelan","sequence":"additional","affiliation":[{"name":"RCSI University of Medicine and Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6915-9015","authenticated-orcid":false,"given":"Adam S.","family":"Butterworth","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK"},{"name":"National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slav\u00e9","family":"Petrovski","sequence":"additional","affiliation":[{"name":"Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Danesh","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK"},{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis S.","family":"Collins","sequence":"additional","affiliation":[{"name":"Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Nag","sequence":"additional","affiliation":[{"name":"Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7839-9467","authenticated-orcid":false,"given":"Brian G.","family":"Drew","sequence":"additional","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia"},{"name":"Molecular Metabolism & Ageing Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia"},{"name":"CRISPR Validation Platform, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua C.","family":"Denny","sequence":"additional","affiliation":[{"name":"Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA"},{"name":"All of Us Research Program, National Institutes of Health, Bethesda, MD, 20892, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk S.","family":"Paul","sequence":"additional","affiliation":[{"name":"Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8222-008X","authenticated-orcid":false,"given":"Samuel A.","family":"Lambert","sequence":"additional","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Inouye","sequence":"additional","affiliation":[{"name":"Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK"},{"name":"British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026080804050534000_2026.08.04.26359685v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586023-06592-6"},{"key":"2026080804050534000_2026.08.04.26359685v1.2","first-page":"19","article-title":"Genetics meets proteomics: perspectives for large population-based studies","volume":"22","year":"2020","journal-title":"Nat. Rev. Genet"},{"key":"2026080804050534000_2026.08.04.26359685v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.10.045"},{"key":"2026080804050534000_2026.08.04.26359685v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03142-z"},{"key":"2026080804050534000_2026.08.04.26359685v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03164-7"},{"key":"2026080804050534000_2026.08.04.26359685v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20241-w"},{"key":"2026080804050534000_2026.08.04.26359685v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3367"},{"key":"2026080804050534000_2026.08.04.26359685v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3506"},{"key":"2026080804050534000_2026.08.04.26359685v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/S41588-022-01168-Y"},{"key":"2026080804050534000_2026.08.04.26359685v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06547-x"},{"key":"2026080804050534000_2026.08.04.26359685v1.11","doi-asserted-by":"crossref","unstructured":"Pietzner, M. et al. Mapping the proteo-genomic convergence of human diseases. Science 374, (2021).","DOI":"10.1126\/science.abj1541"},{"key":"2026080804050534000_2026.08.04.26359685v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05844-9"},{"key":"2026080804050534000_2026.08.04.26359685v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01051-w"},{"key":"2026080804050534000_2026.08.04.26359685v1.14","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.029536"},{"key":"2026080804050534000_2026.08.04.26359685v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35677-5"},{"key":"2026080804050534000_2026.08.04.26359685v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/J.JACC.2023.09.804\/SUPPL_FILE\/MMC1.DOCX"},{"key":"2026080804050534000_2026.08.04.26359685v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35677-5"},{"key":"2026080804050534000_2026.08.04.26359685v1.18","first-page":"357","article-title":"Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights into Cardiovascular Disease","volume":"145","year":"2021","journal-title":"Circulation"},{"key":"2026080804050534000_2026.08.04.26359685v1.19","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1038\/s44161-024-00567-0","article-title":"Integrative proteomic analyses across common cardiac diseases yield mechanistic insights and enhanced prediction","volume":"3","year":"2024","journal-title":"Nature Cardiovascular Research"},{"key":"2026080804050534000_2026.08.04.26359685v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3314"},{"key":"2026080804050534000_2026.08.04.26359685v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07316-0"},{"key":"2026080804050534000_2026.08.04.26359685v1.22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1128"},{"key":"2026080804050534000_2026.08.04.26359685v1.23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsr1809937"},{"key":"2026080804050534000_2026.08.04.26359685v1.24","doi-asserted-by":"publisher","DOI":"10.64898\/2026.05.15.26353298"},{"key":"2026080804050534000_2026.08.04.26359685v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06563-x"},{"key":"2026080804050534000_2026.08.04.26359685v1.26","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1016\/S0140-6736(17)31928-1","article-title":"Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors","volume":"390","year":"2017","journal-title":"The Lancet"},{"key":"2026080804050534000_2026.08.04.26359685v1.27","doi-asserted-by":"crossref","unstructured":"Shuey, M. M. et al. Next-generation phenotyping: introducing phecodeX for enhanced discovery research in medical phenomics. Bioinformatics 39, (2023).","DOI":"10.1093\/bioinformatics\/btad655"},{"key":"2026080804050534000_2026.08.04.26359685v1.28","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1001\/jamacardio.2022.0987","article-title":"Lipoprotein(a) and its Significance in Cardiovascular Disease: A Review","volume":"7","year":"2022","journal-title":"JAMA Cardiol"},{"key":"2026080804050534000_2026.08.04.26359685v1.29","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1001\/jamacardio.2019.0886","article-title":"Effect of the PCSK9 Inhibitor Evolocumab on Total Cardiovascular Events in Patients With Cardiovascular Disease: A Prespecified Analysis From the FOURIER Trial","volume":"4","year":"2019","journal-title":"JAMA Cardiol"},{"key":"2026080804050534000_2026.08.04.26359685v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.10.027"},{"key":"2026080804050534000_2026.08.04.26359685v1.31","doi-asserted-by":"crossref","unstructured":"Wade, F. , Belhaj, K. & Poizat, C . Protein tyrosine phosphatases in cardiac physiology and pathophysiology. Heart Fail. Rev. 23, 261 (2018).","DOI":"10.1007\/s10741-018-9676-1"},{"key":"2026080804050534000_2026.08.04.26359685v1.32","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011494"},{"key":"2026080804050534000_2026.08.04.26359685v1.33","doi-asserted-by":"crossref","unstructured":"Domouzoglou, E. M. et al. Fibroblast growth factors in cardiovascular disease: The emerging role of FGF21. Am. J. Physiol. Heart Circ. Physiol. 309, H1029 (2015).","DOI":"10.1152\/ajpheart.00527.2015"},{"key":"2026080804050534000_2026.08.04.26359685v1.34","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01714-w"},{"key":"2026080804050534000_2026.08.04.26359685v1.35","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1093\/eurheartj\/ehaf045","article-title":"Fibroblast growth factor 5: a novel biomarker for familial hypercholesterolaemia","volume":"46","year":"2025","journal-title":"Eur. Heart J"},{"key":"2026080804050534000_2026.08.04.26359685v1.36","doi-asserted-by":"crossref","first-page":"105437","DOI":"10.1016\/j.isci.2022.105437","article-title":"Ischemic Stroke Impacts the Gut Microbiome, Ileal Epithelial and Immune Homeostasis","volume":"25","year":"2022","journal-title":". iScience"},{"key":"2026080804050534000_2026.08.04.26359685v1.37","doi-asserted-by":"crossref","unstructured":"Abdulrahim, J. W. et al. Epigenome-Wide Association Study for All-Cause Mortality in a Cardiovascular Cohort Identifies Differential Methylation in Castor Zinc Finger 1 (CASZ1). J. Am. Heart Assoc. 8, (2019).","DOI":"10.1161\/JAHA.119.013228"},{"key":"2026080804050534000_2026.08.04.26359685v1.38","doi-asserted-by":"crossref","unstructured":"Zhu, M. et al. Calsyntenin-1 Promotes Doxorubicin-induced Dilated Cardiomyopathy in Rats. Cardiovasc. Drugs Ther. 38, 237 (2022).","DOI":"10.1007\/s10557-022-07389-x"},{"key":"2026080804050534000_2026.08.04.26359685v1.39","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1161\/CIRCRESAHA.120.317144","article-title":"Over-Expression of Intestinal Alkaline Phosphatase Attenuates Atherosclerosis","volume":"128","year":"2021","journal-title":"Circ. Res"},{"key":"2026080804050534000_2026.08.04.26359685v1.40","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/jth.14404","article-title":"The endothelial lectin clearance receptor CLEC4M binds and internalizes factor VIII in a VWF-dependent and independent manner","volume":"17","year":"2019","journal-title":"Journal of Thrombosis and Haemostasis"},{"key":"2026080804050534000_2026.08.04.26359685v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01891-3"},{"key":"2026080804050534000_2026.08.04.26359685v1.42","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2031049"},{"key":"2026080804050534000_2026.08.04.26359685v1.43","doi-asserted-by":"crossref","unstructured":"Uhl\u00e9n, M. et al. Transcriptomics resources of human tissues and organs. Mol. Syst. Biol. 12, 862 (2016).","DOI":"10.15252\/msb.20155865"},{"key":"2026080804050534000_2026.08.04.26359685v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07465-2"},{"key":"2026080804050534000_2026.08.04.26359685v1.45","doi-asserted-by":"crossref","unstructured":"Pihl, R. et al. ITIH4 acts as a protease inhibitor by a novel inhibitory mechanism. Sci. Adv. 7, (2021).","DOI":"10.1126\/sciadv.aba7381"},{"key":"2026080804050534000_2026.08.04.26359685v1.46","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.7589953"},{"key":"2026080804050534000_2026.08.04.26359685v1.47","doi-asserted-by":"crossref","unstructured":"Sp\u00e4th, E. et al. Proteome dynamics reveal Leiomodin 1 as a key regulator of myogenic differentiation. Elife 14, (2025).","DOI":"10.7554\/eLife.104331.3"},{"key":"2026080804050534000_2026.08.04.26359685v1.48","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.090266"},{"key":"2026080804050534000_2026.08.04.26359685v1.49","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-216473"},{"key":"2026080804050534000_2026.08.04.26359685v1.50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007755"},{"key":"2026080804050534000_2026.08.04.26359685v1.51","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.bbadis.2016.11.023","article-title":"FOXOs in the impaired heart: New therapeutic targets for cardiac diseases","volume":"1863","year":"2017","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"},{"key":"2026080804050534000_2026.08.04.26359685v1.52","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307893"},{"key":"2026080804050534000_2026.08.04.26359685v1.53","doi-asserted-by":"crossref","first-page":"107555","DOI":"10.1016\/j.vph.2025.107555","article-title":"Leiomodin 1 haploinsufficiency promotes smooth muscle cell proliferation and increases neointimal lesion size","volume":"161","year":"2025","journal-title":"Vascul. Pharmacol"},{"key":"2026080804050534000_2026.08.04.26359685v1.54","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07148-y"},{"key":"2026080804050534000_2026.08.04.26359685v1.55","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02429-x"},{"key":"2026080804050534000_2026.08.04.26359685v1.56","doi-asserted-by":"crossref","first-page":"205","DOI":"10.2337\/db25-0772","article-title":"Development and Validation of a Type 1 Diabetes Multi-Ancestry Polygenic Score","volume":"75","year":"2026","journal-title":"Diabetes"},{"key":"2026080804050534000_2026.08.04.26359685v1.57","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0579-z"},{"key":"2026080804050534000_2026.08.04.26359685v1.58","doi-asserted-by":"crossref","unstructured":"Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015).","DOI":"10.1186\/s13742-015-0047-8"},{"key":"2026080804050534000_2026.08.04.26359685v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.017."},{"key":"2026080804050534000_2026.08.04.26359685v1.60","doi-asserted-by":"crossref","unstructured":"Moore, C. et al. The INTERVAL trial to determine whether intervals between blood donations can be safely and acceptably decreased to optimise blood supply: study protocol for a randomised controlled trial. Trials 15, 363 (2014).","DOI":"10.1186\/1745-6215-15-363"},{"key":"2026080804050534000_2026.08.04.26359685v1.61","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2354"},{"key":"2026080804050534000_2026.08.04.26359685v1.62","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6945"},{"key":"2026080804050534000_2026.08.04.26359685v1.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.10.042"},{"key":"2026080804050534000_2026.08.04.26359685v1.64","doi-asserted-by":"crossref","unstructured":"Lundberg, M. , Eriksson, A. , Tran, B. , Assarsson, E. & Fredriksson, S . Homogeneous antibody-based proximity extension assays provide sensitive and specific detection of low-abundant proteins in human blood. Nucleic Acids Res. 39 ( 15 ), (2011).","DOI":"10.1093\/nar\/gkr424"},{"key":"2026080804050534000_2026.08.04.26359685v1.65","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1038\/s42255-020-00287-2","article-title":"Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals","volume":"2","year":"2020","journal-title":"Nat. Metab"},{"key":"2026080804050534000_2026.08.04.26359685v1.66","unstructured":"Bick, A. G. et al. Genomic data in the All of Us Research Program. Nature 627, 340 (2024)."},{"key":"2026080804050534000_2026.08.04.26359685v1.67","unstructured":"Hail Team. Hail 0.2.13-81ab564db2b4. https:\/\/github.com\/hail-is\/hail\/releases\/tag\/0.2.13."},{"key":"2026080804050534000_2026.08.04.26359685v1.68","unstructured":"Auton, A. et al. A global reference for human genetic variation. Nature 526, 68 (2015)."},{"key":"2026080804050534000_2026.08.04.26359685v1.69","doi-asserted-by":"publisher","DOI":"10.1038\/ng1847"},{"key":"2026080804050534000_2026.08.04.26359685v1.70","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.21105\/joss.01317","article-title":"lifelines: survival analysis in Python","volume":"4","year":"2019","journal-title":"J. Open Source Softw"},{"key":"2026080804050534000_2026.08.04.26359685v1.71","doi-asserted-by":"crossref","unstructured":"Tran, T. C. et al. PheWAS analysis on large-scale biobank data with PheTK. Bioinformatics 41, (2024).","DOI":"10.1093\/bioinformatics\/btae719"},{"key":"2026080804050534000_2026.08.04.26359685v1.72","doi-asserted-by":"crossref","unstructured":"Schwarzer, G. , Carpenter, J. R. & R\u00fccker, G . Meta-Analysis with R. Cham: Springer 4784, (2015).","DOI":"10.1007\/978-3-319-21416-0"},{"key":"2026080804050534000_2026.08.04.26359685v1.73","doi-asserted-by":"publisher","DOI":"10.1101\/gr.278378.123"},{"key":"2026080804050534000_2026.08.04.26359685v1.74","unstructured":"Van der Auwera, G. A. & O\u2019Connor, B. D . Genomics in the Cloud: Using Docker, GATK, and WDL in Terra . O\u2019Reilly Media (2020)."},{"key":"2026080804050534000_2026.08.04.26359685v1.75","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.116"},{"key":"2026080804050534000_2026.08.04.26359685v1.76","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa152"},{"key":"2026080804050534000_2026.08.04.26359685v1.77","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"2026080804050534000_2026.08.04.26359685v1.78","doi-asserted-by":"publisher","DOI":"10.2196\/14325"},{"key":"2026080804050534000_2026.08.04.26359685v1.79","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1132"},{"key":"2026080804050534000_2026.08.04.26359685v1.80","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz365"},{"key":"2026080804050534000_2026.08.04.26359685v1.81","doi-asserted-by":"crossref","unstructured":"Pliatsika, V. & Rigoutsos, I . \u201cOff-Spotter\u201d: very fast and exhaustive enumeration of genomic lookalikes for designing CRISPR\/Cas guide RNAs. Biol. Direct 10:4, (2015).","DOI":"10.1186\/s13062-015-0035-z"},{"key":"2026080804050534000_2026.08.04.26359685v1.82","doi-asserted-by":"crossref","unstructured":"Bond, S. T. et al. Tissue-specific expression of Cas9 has no impact on whole-body metabolism in four transgenic mouse lines. Mol. Metab. 53, (2021).","DOI":"10.1016\/j.molmet.2021.101292"},{"issue":"1","key":"2026080804050534000_2026.08.04.26359685v1.83","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1038\/s41467-025-57299-3","article-title":"Mitochondrial damage in muscle specific PolG mutant mice activates the integrated stress response and disrupts the mitochondrial folate cycle","volume":"16","year":"2025","journal-title":"Nat. Commun"},{"issue":"23","key":"2026080804050534000_2026.08.04.26359685v1.84","doi-asserted-by":"crossref","first-page":"e15869","DOI":"10.14814\/phy2.15869","article-title":"Deletion of the muscle enriched lncRNA Oip5os1 induces atrial dysfunction in male mice with diabetes","volume":"11","year":"2023","journal-title":"Physiol. Rep"},{"key":"2026080804050534000_2026.08.04.26359685v1.85","doi-asserted-by":"crossref","unstructured":"Zhuang, A. et al. SOD2 in skeletal muscle: New insights from an inducible deletion model. Redox Biol. 47, (2021).","DOI":"10.1016\/j.redox.2021.102135"},{"key":"2026080804050534000_2026.08.04.26359685v1.86","doi-asserted-by":"crossref","unstructured":"Bond, S. T. et al. Deletion of Trim28 in committed adipocytes promotes obesity but preserves glucose tolerance. Nat. Commun. 12 ( 1 ), 74 (2021).","DOI":"10.1038\/s41467-020-20434-3"},{"issue":"8","key":"2026080804050534000_2026.08.04.26359685v1.87","doi-asserted-by":"crossref","first-page":"e3003349","DOI":"10.1371\/journal.pbio.3003349","article-title":"Alterations in ether lipid metabolism in obesity revealed by systems genomics of multi-omics datasets","volume":"23","year":"2025","journal-title":"PLoS Biol"},{"key":"2026080804050534000_2026.08.04.26359685v1.88","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.chembiol.2018.10.008","article-title":"High-Throughput Plasma Lipidomics: Detailed Mapping of the Associations with Cardiometabolic Risk Factors","volume":"26","year":"2019","journal-title":"Cell Chem. Biol"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.08.04.26359685","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T11:05:19Z","timestamp":1786187119000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.08.04.26359685"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":88,"URL":"https:\/\/doi.org\/10.64898\/2026.08.04.26359685","relation":{},"subject":[],"published":{"date-parts":[[2026,8,6]]},"subtype":"preprint"}}