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Dyslipidemia, infla...
Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
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- Chen, H.Y. (författare)
- Division of Experimental Medicine, McGill University, Montreal, Canada; Preventive and Genomic Cardiology, McGill University Health Centre and Research Institute, Room D05.5120, 1001 Decarie Blvd., QC, Montreal, Canada,McGill University,deCODE genetics/Amgen Inc., Reykjavik, Iceland
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- Martinsson, A. (författare)
- Gothenburg University,Göteborgs universitet,Lund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA,Department of Cardiology, Clinical Sciences, Lund University, Sweden; Skåne University Hospital, Lund, Sweden; Wallenberg Laboratory/Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Thanassoulis, G. (författare)
- Division of Experimental Medicine, McGill University, Montreal, Canada; Preventive and Genomic Cardiology, McGill University Health Centre and Research Institute, Room D05.5120, 1001 Decarie Blvd., QC, Montreal, Canada,McGill University
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- Dina, Christian (författare)
- CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes F, France
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- Shaffer, Christian M. (författare)
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, USA
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- Levinson, Rebecca T. (författare)
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, USA
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- Helgadóttir, Anna (författare)
- deCODE genetics/Amgen Inc., Reykjavik, Iceland
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- Capoulade, Romain (författare)
- CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes F, France
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- Munter, Hans Markus (författare)
- McGill University and Genome Quebec Innovation Centre, Montreal, Canada
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- Cairns, Benjamin J. (författare)
- MRC Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
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- Trudsø, Linea C. (författare)
- Laboratory for Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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- Hoekstra, Mary (författare)
- Division of Experimental Medicine, McGill University, Room EM1.2218, 1001 Decarie Blvd., QC, Montreal, Canada; Preventive and Genomic Cardiology, McGill University Health Centre and Research Institute, Montreal, Canada
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- Burr, Hannah A. (författare)
- Division of Experimental Medicine, McGill University, Room EM1.2218, 1001 Decarie Blvd., QC, Montreal, Canada; Preventive and Genomic Cardiology, McGill University Health Centre and Research Institute, Montreal, Canada
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- Marsh, Thomas W. (författare)
- Preventive and Genomic Cardiology, McGill University Health Centre and Research Institute, Room D05.5120, 1001 Decarie Blvd., QC, Montreal, Canada; Department of Human Genetics, McGill University, Montreal, Canada
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- Damrauer, Scott M. (författare)
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
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- Dufresne, Line (författare)
- Preventive and Genomic Cardiology, McGill University Health Centre and Research Institute, Montreal, Canada
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- Le Scouarnec, Solena (författare)
- CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes F, France
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- Messika-Zeitoun, David (författare)
- Department of Cardiology, Bichat Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France; Division of Cardiology, University of Ottawa Heart Institute, ON, Ottawa, Canada
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- Ranatunga, Dilrini K. (författare)
- Division of Research, Kaiser Permanente of Northern California, Oakland, USA
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- Whitmer, Rachel A. (författare)
- Department of Public Health Sciences, University of California Davis, Davis, USA
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- Bonnefond, Amélie (författare)
- University Lille, Inserm, CNRS, Institut Pasteur de Lille, CHU Lille, Lille, France; Department of Metabolism, Imperial College London, London, UK
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- Sveinbjornsson, Garðar (författare)
- deCODE genetics/Amgen Inc., Reykjavik, Iceland
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- Daníelsen, Ragnar (författare)
- Internal Medicine and Emergency Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland
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- Arnar, David O. (författare)
- deCODE genetics/Amgen Inc., Reykjavik, Iceland; Internal Medicine and Emergency Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland; School of Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
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- Thorsteinsdottir, Unnur (författare)
- deCODE genetics/Amgen Inc., Reykjavik, Iceland; School of Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
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- Gudbjartsson, Daníel F (författare)
- deCODE genetics/Amgen Inc., Reykjavik, Iceland; School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland
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- Ghouse, Jonas (författare)
- Laboratory for Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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- Olesen, Morten Salling (författare)
- Laboratory for Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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- Christensen, Alex H. (författare)
- Laboratory for Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen, Denmark
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- Mikkelsen, Susan (författare)
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
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- Jacobsen, Rikke Louise (författare)
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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- Dowsett, Joseph (författare)
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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- Pedersen, Ole Birger Vesterager (författare)
- Department of Clinical Immunology, Zealand University Hospital, Naestved, Denmark
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- Erikstrup, Christian (författare)
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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- Ostrowski, Sisse R. (författare)
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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- O'Donnell, Christopher J. (författare)
- National Heart, Lung, Blood Institute's and Boston University's Framingham Heart Study, Boston, USA
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- Budoff, Matthew J. (författare)
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, USA
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- Gudnason, Vilmundur (författare)
- Faculty of Medicine, University of Iceland, Reykjavík, Iceland
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- Söderberg, Stefan (författare)
- Umeå universitet,Institutionen för folkhälsa och klinisk medicin
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- Rotter, Jerome I. (författare)
- Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, USA
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- Lathrop, Mark (författare)
- McGill University and Genome Quebec Innovation Centre, Montreal, Canada; Department of Human Genetics, McGill University, Montreal, Canada
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- Bundgaard, Henning (författare)
- Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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- Johansson, Bengt (författare)
- Umeå universitet,Institutionen för folkhälsa och klinisk medicin
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- Ljungberg, Johan (författare)
- Umeå universitet,Institutionen för folkhälsa och klinisk medicin
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- Näslund, Ulf (författare)
- Umeå universitet,Institutionen för folkhälsa och klinisk medicin
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- Le Tourneau, Thierry (författare)
- CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes F, France
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- Smith, J. Gustav, 1982 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Wells, Quinn S. (författare)
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, USA
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- Stefánsson, Kári (författare)
- deCODE genetics/Amgen Inc., Reykjavik, Iceland; School of Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
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- Schott, Jean-Jacques (författare)
- CHU Nantes, CNRS, INSERM, l'institut du thorax, 8 Quai Moncousu, Nantes F, France
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- Rader, Daniel J. (författare)
- Departments of Genetics and Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
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- Clarke, Robert (författare)
- MRC Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
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- Engert, James C. (författare)
- Division of Experimental Medicine, McGill University, Montreal, Canada; Preventive and Genomic Cardiology, McGill University Health Centre and Research Institute, Room D05.5120, 1001 Decarie Blvd., QC, Montreal, Canada; Department of Human Genetics, McGill University, Montreal, Canada
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Division of Experimental Medicine, McGill University, Montreal, Canada; Preventive and Genomic Cardiology, McGill University Health Centre and Research Institute, Room D055120, 1001 Decarie Blvd., QC, Montreal, Canada McGill University (creator_code:org_t)
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- Oxford University Press, 2023
- 2023
- Engelska 13 s.
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1927-1939
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://gup.ub.gu.se...
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Abstract
Ämnesord
Stäng
- Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
Ämnesord
- 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)
Nyckelord
- Aortic stenosis
- Gene expression
- Genetic risk score
- Genome-wide association study
- Mendelian randomization
- Phenome-wide association study
- Adiposity
- Aortic Valve Stenosis
- Apolipoproteins
- Dyslipidemias
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Inflammation
- Mendelian Randomization Analysis
- Obesity
- Polymorphism, Single Nucleotide
- Risk Factors
- actin related protein 2
- alkaline phosphatase
- apolipoprotein B
- C reactive protein
- calcium
- gamma glutamyltransferase
- interleukin 6
- lipoprotein
- lipoprotein A
- low density lipoprotein cholesterol
- Notch4 receptor
- sortilin
- triacylglycerol
- apolipoprotein
- aortic stenosis
- aortic valve
- area under the curve
- Article
- body mass
- calcification
- cohort analysis
- coronary artery disease
- differential gene expression
- dyslipidemia
- fasting blood glucose level
- gene expression
- gene linkage disequilibrium
- gene locus
- gene ontology
- gene set enrichment analysis
- genetic risk score
- genome-wide association study
- human
- inflammation
- KEGG
- lipid metabolism
- logistic regression analysis
- major clinical study
- Mendelian randomization analysis
- obesity
- pathogenicity
- phenome wide association study
- phenotype
- quality control
- receiver operating characteristic
- risk factor
- single nucleotide polymorphism
- smoking
- systolic blood pressure
- adipose tissue inflammation
- aortic valve stenosis
- complication
- genetic predisposition
- genetics
- meta analysis
- procedures
- Aortic stenosis
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- ref (ämneskategori)
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- Av författaren/redakt...
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Chen, H.Y.
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Martinsson, A.
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Thanassoulis, G.
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Dina, Christian
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Shaffer, Christi ...
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Levinson, Rebecc ...
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Helgadóttir, Ann ...
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Capoulade, Romai ...
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Munter, Hans Mar ...
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Cairns, Benjamin ...
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Trudsø, Linea C.
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Hoekstra, Mary
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Burr, Hannah A.
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Marsh, Thomas W.
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Damrauer, Scott ...
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Dufresne, Line
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Le Scouarnec, So ...
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Messika-Zeitoun, ...
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Ranatunga, Dilri ...
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Whitmer, Rachel ...
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Bonnefond, Améli ...
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Sveinbjornsson, ...
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Daníelsen, Ragna ...
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Arnar, David O.
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Thorsteinsdottir ...
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Gudbjartsson, Da ...
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Ghouse, Jonas
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Olesen, Morten S ...
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Christensen, Ale ...
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Mikkelsen, Susan
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Jacobsen, Rikke ...
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Dowsett, Joseph
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Pedersen, Ole Bi ...
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Erikstrup, Chris ...
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Ostrowski, Sisse ...
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O'Donnell, Chris ...
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Budoff, Matthew ...
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Gudnason, Vilmun ...
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Söderberg, Stefa ...
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Rotter, Jerome I ...
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Lathrop, Mark
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Bundgaard, Henni ...
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Johansson, Bengt
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Ljungberg, Johan
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Näslund, Ulf
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Le Tourneau, Thi ...
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Smith, J. Gustav ...
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Wells, Quinn S.
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Stefánsson, Kári
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Schott, Jean-Jac ...
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Rader, Daniel J.
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Clarke, Robert
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Engert, James C.
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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
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Medicinsk geneti ...
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European Heart J ...
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