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Cystatin C and Card...
Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study
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- van der Laan, Sander W. (author)
- Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.
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- Fall, Tove (author)
- Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab
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- Soumare, Aicha (author)
- Univ Bordeaux, INSERM, U1219, Team Vintage, Bordeaux, France.
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show more...
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- Teumer, Alexander (author)
- Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany.;German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.
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- Sedaghat, Sanaz (author)
- Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.,UCL, Inst Cardiovasc Sci, Genet Epidemiol Res Grp, London, England.;Barts Heart Ctr, London, England.;UCL, Farr Inst Hlth Informat, London, England.
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- Baumert, Jens (author)
- German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
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- Zabaneh, Delilah (author)
- UCL, Dept Genet Environm & Evolut, London, England.;UCL, Genet Inst, London, England.
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- van Setten, Jessica (author)
- Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.
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- Isgum, Ivana (author)
- Univ Med Ctr Utrecht, Image Sci Inst, Utrecht, Netherlands.,Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands.
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- Galesloot, Tessel E. (author)
- Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.
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- Arpegard, Johannes (author)
- Karolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Stockholm, Sweden.
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- Amouyel, Philippe (author)
- Univ Lille, INSERM, Lille, France.;Inst Pasteur, Lille, France.
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- Trompet, Stella (author)
- Leiden Univ, Med Ctr, Dept Cardiol P C5, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands.
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- Waldenberger, Melanie (author)
- German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
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- Doerr, Marcus (author)
- German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.
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- Magnusson, Patrik K. (author)
- Karolinska Institutet,Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
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- Giedraitis, Vilmantas (author)
- Uppsala universitet,Geriatrik
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- Larsson, Anders (author)
- Uppsala universitet,Biokemisk struktur och funktion,Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.
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- Morris, Andrew P. (author)
- Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
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- Felix, Janine F. (author)
- Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
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- Morrison, Alanna C. (author)
- Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.
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- Franceschini, Nora (author)
- Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
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- Bis, Joshua C. (author)
- Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
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- Kavousi, Maryam (author)
- Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
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- O'Donnell, Christopher (author)
- Boston Vet Adm Healthcare, Dept Cardiol, West Roxbury, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA.
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- Drenos, Fotios (author)
- UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
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- Tragante, Vinicius (author)
- Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.
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- Munroe, Patricia B. (author)
- Queen Mary Univ London, William Harvey Res Inst, Natl Inst Hlth Res, Cardiovasc Biomed Res Unit, London, England.
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- Malik, Rainer (author)
- Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.
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- Dichgans, Martin (author)
- Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.;Munich Cluster Syst Neurol SyNergy, Munich, Germany.
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- Worrall, Bradford B. (author)
- Univ Virginia, Dept Neurol, Charlottesville, VA USA.;Univ Virginia, Dept Hlth Evaluat Sci, Charlottesville, VA USA.
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- Erdmann, Jeanette (author)
- Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany.
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- Nelson, Christopher P. (author)
- Univ Leicester, Glenfield Hosp, British Heart Fdn Cardiovasc, Res Ctr,Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, Natl Inst Hlth Res Leicester, Cardiovasc Biomed Res Unit, Leicester, Leics, England.
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- Samani, Nilesh J. (author)
- Univ Leicester, Glenfield Hosp, British Heart Fdn Cardiovasc, Res Ctr,Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, Natl Inst Hlth Res Leicester, Cardiovasc Biomed Res Unit, Leicester, Leics, England.
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- Schunkert, Heribert (author)
- Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;German Ctr Cardiovasc Res, DZHK, Munich Heart Alliance, Partner Site, Munich, Germany.
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- Marchini, Jonathan (author)
- Univ Oxford, Dept Stat, Oxford, England.
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- Patel, Riyaz S. (author)
- Karolinska Institutet
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- Hingorani, Aroon D. (author)
- UCL, Inst Cardiovasc Sci, Genet Epidemiol Res Grp, London, England.
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- Lind, Lars (author)
- Karolinska Institutet,Uppsala universitet,Kardiovaskulär epidemiologi,Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
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- Pedersen, Nancy L. (author)
- Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
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- de Graaf, Jacqueline (author)
- Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands.
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- Kiemeney, Lambertus A. L. M. (author)
- Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.
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- Baumeister, Sebastian E. (author)
- Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany.;Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany.
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- Franco, Oscar H. (author)
- Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
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- Hofman, Albert (author)
- Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
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- Uitterlinden, Andre G. (author)
- Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
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- Koenig, Wolfgang (author)
- German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany.
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- Meisinger, Christa (author)
- German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
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- Peters, Annette (author)
- German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
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- Thorand, Barbara (author)
- German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
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- Jukema, J. Wouter (author)
- Leiden Univ, Med Ctr, Dept Cardiol P C5, Leiden, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
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- Eriksen, Bjorn Odvar (author)
- UiT Arctic Univ Norway, Metab & Renal Res Grp, Tromso, Norway.;Univ Hosp North Norway, Nephrol Sect, Tromso, Norway.
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- Toft, Ingrid (author)
- Univ Hosp North Norway, Nephrol Sect, Tromso, Norway.
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- Wilsgaard, Tom (author)
- UiT Arctic Univ Norway, Dept Community Med, Tromso, Norway.
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- Onland-Moret, N. Charlotte (author)
- Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
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- van der Schouw, Yvonne T. (author)
- Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
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- Debette, Stephanie (author)
- Univ Bordeaux, INSERM, U1219, Team Vintage, Bordeaux, France.
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- Kumari, Meena (author)
- Univ Essex, Biol & Social Epidemiol, Inst Social & Econ Res, Colchester CO4 3SQ, Essex, England.
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- Svensson, Per (author)
- Karolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Stockholm, Sweden.
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- van der Harst, Pim (author)
- ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
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- Kivimaki, Mika (author)
- UCL, Dept Epidemiol & Publ Hlth, London, England.
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- Keating, Brendan J. (author)
- Univ Penn, Dept Surg, Div Transplantat, Perelman Sch Med, Philadelphia, PA 19104 USA.
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- Sattar, Naveed (author)
- Univ Glasgow, Glasgow, Lanark, Scotland.
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- Dehghan, Abbas (author)
- Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
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- Reiner, Alex P. (author)
- Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
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- Ingelsson, Erik (author)
- Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
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- den Ruijter, Hester M. (author)
- Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.
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- de Bakker, Paul I. W. (author)
- Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands.
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- Pasterkamp, Gerard (author)
- Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.;Univ Med Ctr Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, Utrecht, Netherlands.
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- Ärnlöv, Johan (author)
- Högskolan Dalarna,Uppsala universitet,Kardiovaskulär epidemiologi,Medicinsk vetenskap,Uppsala university
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- Holmes, Michael V. (author)
- Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.
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- Asselbergs, Folkert W. (author)
- Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England.
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Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands Molekylär epidemiologi (creator_code:org_t)
- Elsevier BV, 2016
- 2016
- English.
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 68:9, s. 934-945
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Abstract
Subject headings
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- BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.
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 (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- coronary heart disease
- genetics
- heart failure
- ischemic stroke
- Hälsa och välfärd
Publication and Content Type
- ref (subject category)
- art (subject category)
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van der Laan, Sa ...
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Fall, Tove
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Soumare, Aicha
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Teumer, Alexande ...
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Sedaghat, Sanaz
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Baumert, Jens
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Zabaneh, Delilah
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van Setten, Jess ...
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Isgum, Ivana
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Galesloot, Tesse ...
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Arpegard, Johann ...
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Amouyel, Philipp ...
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Trompet, Stella
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Waldenberger, Me ...
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Doerr, Marcus
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Magnusson, Patri ...
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Giedraitis, Vilm ...
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Larsson, Anders
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Morris, Andrew P ...
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Felix, Janine F.
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Morrison, Alanna ...
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Franceschini, No ...
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Bis, Joshua C.
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Kavousi, Maryam
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O'Donnell, Chris ...
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Drenos, Fotios
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Tragante, Vinici ...
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Munroe, Patricia ...
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Malik, Rainer
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Dichgans, Martin
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Worrall, Bradfor ...
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Erdmann, Jeanett ...
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Nelson, Christop ...
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Samani, Nilesh J ...
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Schunkert, Herib ...
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Marchini, Jonath ...
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Patel, Riyaz S.
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Hingorani, Aroon ...
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Lind, Lars
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Pedersen, Nancy ...
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de Graaf, Jacque ...
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Kiemeney, Lamber ...
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Baumeister, Seba ...
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Franco, Oscar H.
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Hofman, Albert
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Uitterlinden, An ...
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Koenig, Wolfgang
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Meisinger, Chris ...
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Peters, Annette
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Thorand, Barbara
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Jukema, J. Woute ...
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Eriksen, Bjorn O ...
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Toft, Ingrid
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Wilsgaard, Tom
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Onland-Moret, N. ...
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van der Schouw, ...
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Debette, Stephan ...
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Kumari, Meena
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Svensson, Per
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van der Harst, P ...
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Kivimaki, Mika
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Keating, Brendan ...
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Sattar, Naveed
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Dehghan, Abbas
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Reiner, Alex P.
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Ingelsson, Erik
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den Ruijter, Hes ...
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de Bakker, Paul ...
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Pasterkamp, Gera ...
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Ärnlöv, Johan
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Holmes, Michael ...
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Asselbergs, Folk ...
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Uppsala University
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Karolinska Institutet
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Högskolan Dalarna