Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development
Abstract Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44680-3 |
| _version_ | 1797349789702029312 |
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| author | Amil M. Shah Peder L. Myhre Victoria Arthur Pranav Dorbala Humaira Rasheed Leo F. Buckley Brian Claggett Guning Liu Jianzhong Ma Ngoc Quynh Nguyen Kunihiro Matsushita Chiadi Ndumele Adrienne Tin Kristian Hveem Christian Jonasson Håvard Dalen Eric Boerwinkle Ron C. Hoogeveen Christie Ballantyne Josef Coresh Torbjørn Omland Bing Yu |
| author_facet | Amil M. Shah Peder L. Myhre Victoria Arthur Pranav Dorbala Humaira Rasheed Leo F. Buckley Brian Claggett Guning Liu Jianzhong Ma Ngoc Quynh Nguyen Kunihiro Matsushita Chiadi Ndumele Adrienne Tin Kristian Hveem Christian Jonasson Håvard Dalen Eric Boerwinkle Ron C. Hoogeveen Christie Ballantyne Josef Coresh Torbjørn Omland Bing Yu |
| author_sort | Amil M. Shah |
| collection | DOAJ |
| description | Abstract Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants in mid-life and late-life and in Trøndelag Health Study participants identified 37 proteins consistently associated with incident HF independent of traditional risk factors. Mendelian randomization supported causal effects of 10 on HF, HF risk factors, or left ventricular size and function, including matricellular (e.g. SPON1, MFAP4), senescence-associated (FSTL3, IGFBP7), and inflammatory (SVEP1, CCL15, ITIH3) proteins. Protein co-regulation network analyses identified 5 modules associated with HF risk, two of which were influenced by genetic variants that implicated trans hotspots within the VTN and CFH genes. |
| first_indexed | 2024-03-08T12:36:36Z |
| format | Article |
| id | doaj.art-875f4625364e4d5ba8e1f87be100c17c |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T12:36:36Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-875f4625364e4d5ba8e1f87be100c17c2024-01-21T12:27:22ZengNature PortfolioNature Communications2041-17232024-01-0115111810.1038/s41467-023-44680-3Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure developmentAmil M. Shah0Peder L. Myhre1Victoria Arthur2Pranav Dorbala3Humaira Rasheed4Leo F. Buckley5Brian Claggett6Guning Liu7Jianzhong Ma8Ngoc Quynh Nguyen9Kunihiro Matsushita10Chiadi Ndumele11Adrienne Tin12Kristian Hveem13Christian Jonasson14Håvard Dalen15Eric Boerwinkle16Ron C. Hoogeveen17Christie Ballantyne18Josef Coresh19Torbjørn Omland20Bing Yu21Division of Cardiology, University of Texas Southwestern Medical CenterAkershus University Hospital and K.G. Jebsen Center for Cardiac Biomarkers, University of OsloDivision of Cardiology, University of Texas Southwestern Medical CenterDivision of Cardiovascular Medicine, Brigham and Women’s HospitalAkershus University Hospital and K.G. Jebsen Center for Cardiac Biomarkers, University of OsloDepartment of Pharmacy, Brigham and Women’s HospitalDivision of Cardiovascular Medicine, Brigham and Women’s HospitalDepartment of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Sciences Center at HoustonDepartment of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Sciences Center at HoustonDepartment of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Sciences Center at HoustonDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public HealthDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public HealthUniversity of Mississippi Medical CenterDepartment of Public Health and Nursing, HUNT Research Center, Norwegian University of Science and TechnologyDepartment of Public Health and Nursing, HUNT Research Center, Norwegian University of Science and TechnologyDepartment of Circulation and Medical Imaging, Norwegian University of Science and TechnologyDepartment of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Sciences Center at HoustonDivision of Cardiology, Baylor College of MedicineDivision of Cardiology, Baylor College of MedicineDepartments of Medicine and Population Health, NYU Langone HealthAkershus University Hospital and K.G. Jebsen Center for Cardiac Biomarkers, University of OsloDepartment of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Sciences Center at HoustonAbstract Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants in mid-life and late-life and in Trøndelag Health Study participants identified 37 proteins consistently associated with incident HF independent of traditional risk factors. Mendelian randomization supported causal effects of 10 on HF, HF risk factors, or left ventricular size and function, including matricellular (e.g. SPON1, MFAP4), senescence-associated (FSTL3, IGFBP7), and inflammatory (SVEP1, CCL15, ITIH3) proteins. Protein co-regulation network analyses identified 5 modules associated with HF risk, two of which were influenced by genetic variants that implicated trans hotspots within the VTN and CFH genes.https://doi.org/10.1038/s41467-023-44680-3 |
| spellingShingle | Amil M. Shah Peder L. Myhre Victoria Arthur Pranav Dorbala Humaira Rasheed Leo F. Buckley Brian Claggett Guning Liu Jianzhong Ma Ngoc Quynh Nguyen Kunihiro Matsushita Chiadi Ndumele Adrienne Tin Kristian Hveem Christian Jonasson Håvard Dalen Eric Boerwinkle Ron C. Hoogeveen Christie Ballantyne Josef Coresh Torbjørn Omland Bing Yu Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development Nature Communications |
| title | Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development |
| title_full | Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development |
| title_fullStr | Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development |
| title_full_unstemmed | Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development |
| title_short | Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development |
| title_sort | large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development |
| url | https://doi.org/10.1038/s41467-023-44680-3 |
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