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Probing the Virtual...
Probing the Virtual Proteome to Identify Novel Disease Biomarkers
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- Mosley, Jonathan D. (författare)
- Vanderbilt University
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- Benson, Mark D. (författare)
- Brigham and Women's Hospital / Harvard Medical School,Beth Israel Deaconess Medical Center
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- Smith, J. Gustav (författare)
- Lund University,Lunds universitet,Molecular Epidemiology and Cardiology,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital
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- Melander, Olle (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital
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- Ngo, Debby (författare)
- Harvard University,Massachusetts General Hospital
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- Shaffer, Christian M. (författare)
- Vanderbilt University
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- Ferguson, Jane F. (författare)
- Vanderbilt University
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- Herzig, Matthew S. (författare)
- Beth Israel Deaconess Medical Center
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- McCarty, Catherine A. (författare)
- University of Minnesota
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- Chute, Christopher G. (författare)
- Johns Hopkins University
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- Jarvik, Gail P. (författare)
- University of Washington
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- Gordon, Adam S. (författare)
- University of Washington
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- Palmer, Melody R. (författare)
- University of Washington
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- Crosslin, David R. (författare)
- University of Washington
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- Larson, Eric B. (författare)
- Kaiser Permanente Research Institute,University of Washington
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- Carrell, David S. (författare)
- Kaiser Permanente Research Institute
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- Kullo, Iftikhar J. (författare)
- Mayo Clinic Minnesota
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- Pacheco, Jennifer A. (författare)
- Northwestern University
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- Peissig, Peggy L. (författare)
- Marshfield Clinic
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- Brilliant, Murray H. (författare)
- Marshfield Clinic
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- Kitchner, Terrie E. (författare)
- Marshfield Clinic
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- Linneman, James G. (författare)
- Marshfield Clinic
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- Namjou, Bahram (författare)
- University of Cincinnati,Cincinnati Children's Hospital Medical Center
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- Williams, Marc S. (författare)
- Geisinger Health System
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- Ritchie, Marylyn D. (författare)
- University of Pennsylvania
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- Borthwick, Kenneth M. (författare)
- Geisinger Health System
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- Kiryluk, Krzysztof (författare)
- Columbia University
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- Mentch, Frank D. (författare)
- The Children's Hospital of Philadelphia
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- Sleiman, Patrick M. (författare)
- The Children's Hospital of Philadelphia
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- Karlson, Elizabeth W. (författare)
- Harvard University,Brigham and Women's Hospital / Harvard Medical School
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- Verma, Shefali S. (författare)
- University of Pennsylvania
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- Zhu, Yineng (författare)
- Boston University
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- Vasan, Ramachandran S. (författare)
- Boston University
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- Yang, Qiong (författare)
- Boston University
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- Denny, Josh C. (författare)
- Vanderbilt University
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- Roden, Dan M. (författare)
- Vanderbilt University
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- Gerszten, Robert E. (författare)
- Beth Israel Deaconess Medical Center
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- Wang, Thomas J. (författare)
- Vanderbilt University
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(creator_code:org_t)
- 2018
- 2018
- Engelska 13 s.
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Ingår i: Circulation. - 1524-4539. ; 138:22, s. 2469-2481
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- BACKGROUND: Proteomic approaches allow measurement of thousands of proteins in a single specimen, which can accelerate biomarker discovery. However, applying these technologies to massive biobanks is not currently feasible because of the practical barriers and costs of implementing such assays at scale. To overcome these challenges, we used a "virtual proteomic" approach, linking genetically predicted protein levels to clinical diagnoses in >40 000 individuals. METHODS: We used genome-wide association data from the Framingham Heart Study (n=759) to construct genetic predictors for 1129 plasma protein levels. We validated the genetic predictors for 268 proteins and used them to compute predicted protein levels in 41 288 genotyped individuals in the Electronic Medical Records and Genomics (eMERGE) cohort. We tested associations for each predicted protein with 1128 clinical phenotypes. Lead associations were validated with directly measured protein levels and either low-density lipoprotein cholesterol or subclinical atherosclerosis in the MDCS (Malmö Diet and Cancer Study; n=651). RESULTS: In the virtual proteomic analysis in eMERGE, 55 proteins were associated with 89 distinct diagnoses at a false discovery rate q<0.1. Among these, 13 associations involved lipid (n=7) or atherosclerosis (n=6) phenotypes. We tested each association for validation in MDCS using directly measured protein levels. At Bonferroni-adjusted significance thresholds, levels of apolipoprotein E isoforms were associated with hyperlipidemia, and circulating C-type lectin domain family 1 member B and platelet-derived growth factor receptor-β predicted subclinical atherosclerosis. Odds ratios for carotid atherosclerosis were 1.31 (95% CI, 1.08-1.58; P=0.006) per 1-SD increment in C-type lectin domain family 1 member B and 0.79 (0.66-0.94; P=0.008) per 1-SD increment in platelet-derived growth factor receptor-β. CONCLUSIONS: We demonstrate a biomarker discovery paradigm to identify candidate biomarkers of cardiovascular and other diseases.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- atherosclerosis
- biomarkers
- electronic health records
- proteomics
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- Av författaren/redakt...
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Mosley, Jonathan ...
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Benson, Mark D.
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Smith, J. Gustav
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Melander, Olle
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Ngo, Debby
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Shaffer, Christi ...
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visa fler...
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Ferguson, Jane F ...
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Herzig, Matthew ...
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McCarty, Catheri ...
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Chute, Christoph ...
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Jarvik, Gail P.
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Gordon, Adam S.
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Palmer, Melody R ...
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Crosslin, David ...
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Larson, Eric B.
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Carrell, David S ...
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Kullo, Iftikhar ...
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Pacheco, Jennife ...
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Peissig, Peggy L ...
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Brilliant, Murra ...
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Kitchner, Terrie ...
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Linneman, James ...
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Namjou, Bahram
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Williams, Marc S ...
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Ritchie, Marylyn ...
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Borthwick, Kenne ...
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Kiryluk, Krzyszt ...
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Mentch, Frank D.
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Sleiman, Patrick ...
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Karlson, Elizabe ...
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Verma, Shefali S ...
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Zhu, Yineng
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Vasan, Ramachand ...
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Yang, Qiong
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Denny, Josh C.
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Roden, Dan M.
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Gerszten, Robert ...
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Wang, Thomas J.
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
- Artiklar i publikationen
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Circulation
- Av lärosätet
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Lunds universitet