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Plasma proteomics a...
Plasma proteomics and lung function in four community-based cohorts
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- Rydell, Andreas (author)
- Karolinska Institutet
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- Nowak, Christoph (author)
- Karolinska Institutet
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- Janson, Christer (author)
- Uppsala universitet,Lung- allergi- och sömnforskning
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- Lisspers, Karin, Docent, 1954- (author)
- Uppsala universitet,Allmänmedicin och preventivmedicin
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- Ställberg, Björn, Docent (author)
- Uppsala universitet,Allmänmedicin och preventivmedicin
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- Iggman, David (author)
- Uppsala universitet,Klinisk nutrition och metabolism,Region Dalarna, Falun
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- Leppert, Jerzy (author)
- Uppsala universitet,Centrum för klinisk forskning, Västerås
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- Hedberg, Pär (author)
- Uppsala universitet,Centrum för klinisk forskning, Västerås,Hospital of Västmanland, Västerås
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- Sundström, Johan, Professor, 1971- (author)
- Uppsala universitet,Klinisk epidemiologi,University of New South Wales, Sydney, Australia
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- Ingelsson, Erik, 1975- (author)
- Stanford University School of Medicine; Stanford University
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- Lind, Lars (author)
- Uppsala universitet,Klinisk epidemiologi
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- Ärnlöv, Johan (author)
- Karolinska Institutet,Högskolan Dalarna,Medicinsk vetenskap,Karolinska Institute, Huddinge; Region Dalarna, Falun,Karolinska Institutet; Region Dalarna, Falun; Dalarna University, Falun
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- Elsevier, 2021
- 2021
- English.
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In: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 176
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Abstract
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- BACKGROUND: Underlying mechanism leading to impaired lung function are incompletely understood.OBJECTIVES: To investigate whether protein profiling can provide novel insights into mechanisms leading to impaired lung function.METHODS: We used four community-based studies (n = 2552) to investigate associations between 79 cardiovascular/inflammatory proteins and forced expiratory volume in 1 s percent predicted (FEV1%) assessed by spirometry. We divided the cohorts into discovery and replication samples and used risk factor-adjusted linear regression corrected for multiple comparison (false discovery rate of 5%). We performed Mendelian randomization analyses using genetic and spirometry data from the UK Biobank (n = 421,986) to assess causality.MEASUREMENTS AND MAIN RESULTS: In cross-sectional analysis, 22 proteins were associated with lower FEV1% in both the discovery and replication sample, regardless of stratification by smoking status. The combined proteomic data cumulatively explained 5% of the variation in FEV1%. In longitudinal analyses (n = 681), higher plasma levels of growth differentiation factor 15 (GDF-15) and interleukin 6 (IL-6) predicted a more rapid 5-year decline in lung function (change in FEV1% per standard deviation of protein level -1.4, (95% CI, -2.5 to -0.3) for GDF-15, and -0.8, (95% CI, -1.5 to -0.2) for IL-6. Mendelian randomization analysis in UK-biobank provided support for a causal effect of increased GDF-15 levels and reduced FEV1%.CONCLUSIONS: Our combined approach identified GDF-15 as a potential causal factor in the development of impaired lung function in the general population. These findings encourage additional studies evaluating the role of GDF-15 as a causal factor for impaired lung function.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- FEV1
- Mendelian randomization
- Protein expression
- Proteomics
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Rydell, Andreas
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Nowak, Christoph
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Janson, Christer
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Lisspers, Karin, ...
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Ställberg, Björn ...
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Iggman, David
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Leppert, Jerzy
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Hedberg, Pär
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Sundström, Johan ...
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Ingelsson, Erik, ...
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Lind, Lars
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Ärnlöv, Johan
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Respiratory Medi ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
- Articles in the publication
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Respiratory Medi ...
- By the university
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Uppsala University
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Högskolan Dalarna
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Karolinska Institutet