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Genome-wide associa...
Genome-wide association and Mendelian randomization study of NT-proBNP in patients with acute coronary syndrome
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- Johansson, Åsa (author)
- Uppsala universitet,Medicinsk genetik och genomik
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- Eriksson, Niclas (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR)
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- Lindholm, Daniel (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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- Varenhorst, Christoph (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR)
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- James, Stefan (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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- Syvänen, Ann-Christine (author)
- Uppsala universitet,Molekylär medicin
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- Axelsson, Tomas (author)
- Uppsala universitet,Molekylär medicin
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- Siegbahn, Agneta (author)
- Uppsala universitet,Koagulation och inflammationsvetenskap
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- Barratt, Bryan J. (author)
- AstraZeneca R&D, Alderley Pk SK10 4TF, Cheshire, England.
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- Becker, Richard C. (author)
- Acad Hlth Ctr, Div Cardiovasc Hlth & Dis, Heart Lung & Vasc Inst, Cincinnati, OH 45267 USA.
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- Himmelmann, Anders (author)
- AstraZeneca Res & Dev, S-43150 Molndal, Sweden.
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- Katus, Hugo A. (author)
- Univ Klinikum Heidelberg, Med Klin, D-69120 Heidelberg, Germany.
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- Steg, Philippe Gabriel (author)
- INSERM, Unite 1148, F-75019 Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75018 Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, F-75013 Paris, France.;Royal Brompton Hosp, ICMS, NHLI Imperial Coll, London SW3 6NP, England.
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- Storey, Robert F. (author)
- Univ Sheffield, Dept Cardiovasc Sci, Sheffield S10 2RX, S Yorkshire, England.
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- Wallentin, Lars (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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(creator_code:org_t)
- 2016-01-21
- 2016
- English.
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:7, s. 1447-1456
- Related links:
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a strong predictor of mortality in coronary artery disease and is widely employed as a prognostic biomarker. However, a causal relationship between NT-proBNP and clinical endpoints has not been established. We have performed a genome-wide association and Mendelian randomization study of NT-proBNP. We used a discovery set of 3740 patients from the PLATelet inhibition and patient Outcomes (PLATO) trial, which enrolled 18 624 patients with acute coronary syndrome (ACS). A further set of 5492 patients, from the same trial, was used for replication. Genetic variants at two novel loci (SLC39A8 and POC1B/GALNT4) were associated with NT-proBNP levels and replicated together with the previously known NPPB locus. The most significant SNP (rs198389, pooled P = 1.07 x 10(-15)) in NPPB interrupts an E-box consensus motif in the gene promoter. The association in SLC39A8 is driven by a deleterious variant (rs13107325, pooled P = 5.99 x 10(-10)), whereas the most significant SNP in POC1B/GALNT4 (rs11105306, pooled P = 1.02 x 10(-16)) is intronic. The SLC39A8 SNP was associated with higher risk of cardiovascular (CV) death (HR = 1.39, 95% CI: 1.08-1.79, P = 0.0095), but the other loci were not associated with clinical endpoints. We have identified two novel loci to be associated with NT-proBNP in patients with ACS. Only the SLC39A8 variant, but not the NPPB variant, was associated with a clinical endpoint. Due to pleotropic effects of SLC39A8, these results do not suggest that NT-proBNP levels have a direct effect on mortality in ACS patients. PLATO Clinical Trial Registration: ; NCT00391872.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
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- art (subject category)
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- By the author/editor
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Johansson, Åsa
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Eriksson, Niclas
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Lindholm, Daniel
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Varenhorst, Chri ...
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James, Stefan
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Syvänen, Ann-Chr ...
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show more...
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Axelsson, Tomas
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Siegbahn, Agneta
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Barratt, Bryan J ...
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Becker, Richard ...
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Himmelmann, Ande ...
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Katus, Hugo A.
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Steg, Philippe G ...
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Storey, Robert F ...
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Wallentin, Lars
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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 Basic Medicine
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and Medical Genetics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
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Human Molecular ...
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Uppsala University