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Effects of the coro...
Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis
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- Trenkwalder, Teresa (author)
- Technical University of Munich
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- Nelson, Christopher P. (author)
- University of Leicester
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- Musameh, Muntaser D. (author)
- University of Leicester
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- Mordi, Ify R. (author)
- Ninewells Hospital and Medical School,University of Dundee
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- Kessler, Thorsten (author)
- Technical University of Munich
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- Pellegrini, Costanza (author)
- Technical University of Munich
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- Debiec, Radoslaw (author)
- University of Leicester
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- Rheude, Tobias (author)
- Technical University of Munich
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- Lazovic, Viktor (author)
- Technical University of Munich
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- Zeng, Lingyao (author)
- Technical University of Munich
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- Martinsson, Andreas (author)
- Sahlgrenska University Hospital
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- Gustav Smith, J. (author)
- Lund University,Lunds universitet,Cardiovascular Epigenetics,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital
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- Gådin, Jesper R. (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Franco-Cereceda, Anders (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Eriksson, Per (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Nielsen, Jonas B. (author)
- University of Michigan
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- Graham, Sarah E. (author)
- University of Michigan
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- Willer, Cristen J. (author)
- University of Michigan
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- Hveem, Kristian (author)
- Norwegian University of Science and Technology
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- Kastrati, Adnan (author)
- Technical University of Munich,German Centre for Cardiovascular Research
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- Braund, Peter S. (author)
- University of Leicester
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- Palmer, Colin N.A. (author)
- Ninewells Hospital and Medical School,University of Dundee
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- Aracil, Amparo (author)
- Ninewells Hospital and Medical School,University of Dundee
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- Husser, Oliver (author)
- St.-Johannes-Hospital Dortmund,Technical University of Munich
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- Koenig, Wolfgang (author)
- Technical University of Munich,German Centre for Cardiovascular Research
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- Schunkert, Heribert (author)
- German Centre for Cardiovascular Research,Technical University of Munich
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- Lang, Chim C. (author)
- University of Dundee,Ninewells Hospital and Medical School
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- Hengstenberg, Christian (author)
- German Centre for Cardiovascular Research,Medical University of Vienna,Technical University of Munich
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- Samani, Nilesh J. (author)
- University of Leicester
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- English.
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 276, s. 212-217
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Abstract
Subject headings
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- Background: Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. Methods: We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls. Results: In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24–1.52, p = 6.9 × 10−10) with a larger effect size in those without CAD (OR 1.53; 95%CI 1.31–1.79) compared to those with CAD (OR 1.27; 95%CI 1.12–1.45). The CAD-associated allele at 9p21 was associated with a trend towards lower risk of AVS (OR 0.93; 95%CI 0.88–0.99, p = 0.014). External validation confirmed the association of the LPA risk allele with risk of AVS (OR 1.37; 95%CI 1.27–1.47), again with a higher effect size in those without CAD. The small protective effect of the 9p21 CAD risk allele could not be replicated (OR 0.98; 95%CI 0.95–1.02). Conclusions: Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS.
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 -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- 9p21
- Aortic valve stenosis
- Lipoprotein (a)
- Risk factors
- Valvular heart disease
Publication and Content Type
- art (subject category)
- ref (subject category)
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Trenkwalder, Ter ...
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Nelson, Christop ...
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Musameh, Muntase ...
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Mordi, Ify R.
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Kessler, Thorste ...
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Pellegrini, Cost ...
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show more...
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Debiec, Radoslaw
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Rheude, Tobias
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Lazovic, Viktor
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Zeng, Lingyao
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Martinsson, Andr ...
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Gustav Smith, J.
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Gådin, Jesper R.
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Franco-Cereceda, ...
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Eriksson, Per
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Nielsen, Jonas B ...
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Graham, Sarah E.
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Willer, Cristen ...
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Hveem, Kristian
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Kastrati, Adnan
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Braund, Peter S.
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Palmer, Colin N. ...
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Aracil, Amparo
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Husser, Oliver
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Koenig, Wolfgang
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Schunkert, Herib ...
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Lang, Chim C.
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Hengstenberg, Ch ...
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Samani, Nilesh J ...
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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 Basic Medicine
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and Medical Genetics
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Lund University
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Karolinska Institutet