-
Something wrong with this record ?
PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study
AF. Schmidt, DI. Swerdlow, MV. Holmes, RS. Patel, Z. Fairhurst-Hunter, DM. Lyall, FP. Hartwig, BL. Horta, E. Hyppönen, C. Power, M. Moldovan, E. van Iperen, GK. Hovingh, I. Demuth, K. Norman, E. Steinhagen-Thiessen, J. Demuth, L. Bertram, T. Liu,...
Language English Country England, Great Britain
Document type Journal Article
- MeSH
- Diabetes Mellitus, Type 2 blood diagnosis genetics MeSH
- Genetic Predisposition to Disease genetics MeSH
- Genetic Variation genetics MeSH
- Cohort Studies MeSH
- Blood Glucose metabolism MeSH
- Cholesterol, LDL blood genetics MeSH
- Humans MeSH
- Mendelian Randomization Analysis methods MeSH
- Proprotein Convertase 9 genetics MeSH
- Randomized Controlled Trials as Topic methods MeSH
- Case-Control Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. METHODS: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m2, -0·09 to 0·30). INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins. FUNDING: British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.
Anschutz Medical Campus University of Colorado Denver Denver CO USA
Biomedical and Translational Informatics Geisinger Health System Danville PA USA
Bradford Institute for Health Research Bradford Royal Infirmary Bradford UK
Cancer Epidemiology Unit San Giovanni Battista Hospital Turin Italy
Center for Health Research Geisinger Clinic Danville PA USA
Center for Human Genetics Marshfield Clinic Research Foundation Marshfield WI USA
Centre for Cardiovascular Genetics University College London UK
Centre for Oncology Prevention CPO Piemonte Turin Italy
Charité Research Group on Geriatrics Charité Universitätsmedizin Berlin Berlin Germany
Children's Hospital of Philadelphia Philadelphia PA USA
Department of Biomedical Informatics Vanderbilt University School of Medicine Nashville TN USA
Department of Clinical Epidemiology Leiden University Medical Center Leiden Netherlands
Department of Clinical Experimental Research Rigshospitalet Copenhagen Denmark
Department of Epidemiology and Preventive Medicine University of Regensburg Regensburg Germany
Department of Epidemiology Erasmus University Medical Center Rotterdam Netherlands
Department of Genomics of Common Disease Imperial College London London UK
Department of Internal Medicine B University Medicine Greifswald Greifswald Germany
Department of Internal Medicine Erasmus University Medical Center Rotterdam Netherlands
Department of Medical Sciences University of Turin Turin Italy
Department of Medicine A University Medicine Greifswald Greifswald Germany
Department of Medicine Imperial College London London UK
Department of Neurology Medical University of Innsbruck Innsbruck Austria
Department of Primary Care and Population Health University College London UK
Department of Respiratory Medicine Academic Medical Center Amsterdam Netherlands
Department of Surgery Nicosia Medical School University of Nicosia Nicosia Cyprus
Department of Surgery University of Pennsylvania Philadelphia PA USA
Department of Vascular Medicine Academic Medical Center Amsterdam Netherlands
Department of Vascular Surgery Imperial College London London UK
Departments of Medicine and Pharmacology Vanderbilt University School of Medicine Nashville TN USA
Division of Biomedical Statistics and Informatics Mayo Clinic Rochester MN USA
Durrer Center for Cardiovascular Research Netherlands Heart Institute Utrecht Netherlands
E CA Economics GmbH Berlin Germany
Essentia Institute of Rural Health Duluth MN USA
George Washington University Washington DC USA
German Centre for Cardiovascular Research Greifswald Germany
Group Health Research Institute in Seattle WA USA
Group Health Research Institute Seattle WA USA
Human Genetics Foundation HuGeF Turin Italy
I'institut du Thorax INSERM CNRS University of Nantes CHU de Nantes Nantes France
Institute for Community Medicine University Medicine Greifswald Greifswald Germany
Institute for Social and Economic Research University of Essex Colchester Essex UK
Institute of Cardiovascular and Medical Sciences University of Glasgow Glasgow UK
Institute of Cardiovascular Science University College London UK
Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UK
Institute of Health and Wellbeing University of Glasgow Glasgow UK
Institute of Medical and Human Genetics Charité Universitätsmedizin Berlin Berlin Germany
Internal Medicine Unit Department of Medicine Lausanne University Hospital Lausanne Switzerland
Jagiellonian University Collegium Medicum Krakow Poland
Lithuanian University of Health Sciences Kaunas Lithuania
Max Planck Institute for Human Development Berlin Germany
Max Planck Institute for Molecular Genetics Berlin Germany
Molecular Epidemiology Department of Medical Sciences Uppsala University Uppsala Sweden
National Institute of Public Health Prague Czech Republic
Neuroepidemiology and Ageing Research Unit Imperial College London London UK
Novosibirsk State Medical University Novosibirsk Russia
Population Health Research Institute Hamilton ON Canada
Population Health Research Institute St George's University of London London UK
Population Policy and Practice UCL Great Ormond Street Institute of Child Health London UK
Postgraduate Program in Epidemiology Federal University of Pelotas Pelotas Brazil
Research Centre for Prevention and Health Capital Region of Denmark Denmark
Robertson Centre for Biostatistics University of Glasgow Glasgow UK
School of Health Sciences University of South Australia Adelaide SA Australia
School of Social and Community Medicine University of Bristol Bristol UK
Science for Life Laboratory Department of Medical Sciences Uppsala University Uppsala Sweden
South Australian Health and Medical Research Institute Adelaide SA Australia
South Australian Health and Medical Research Institute EMBL Australia Adelaide SA Australia
The Barts Heart Centre St Bartholomew's Hospital London UK
University of Newcastle Newcastle NSW Australia
Wellcome Trust Centre for Human Genetics University of Oxford Oxford UK
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc18025241
- 003
- CZ-PrNML
- 005
- 20180718112724.0
- 007
- ta
- 008
- 180709s2017 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/S2213-8587(16)30396-5 $2 doi
- 035 __
- $a (PubMed)27908689
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Schmidt, Amand F $u Institute of Cardiovascular Science, University College London, UK; Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, UK. Electronic address: amand.schmidt@ucl.ac.uk.
- 245 10
- $a PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study / $c AF. Schmidt, DI. Swerdlow, MV. Holmes, RS. Patel, Z. Fairhurst-Hunter, DM. Lyall, FP. Hartwig, BL. Horta, E. Hyppönen, C. Power, M. Moldovan, E. van Iperen, GK. Hovingh, I. Demuth, K. Norman, E. Steinhagen-Thiessen, J. Demuth, L. Bertram, T. Liu, S. Coassin, J. Willeit, S. Kiechl, K. Willeit, D. Mason, J. Wright, R. Morris, G. Wanamethee, P. Whincup, Y. Ben-Shlomo, S. McLachlan, JF. Price, M. Kivimaki, C. Welch, A. Sanchez-Galvez, P. Marques-Vidal, A. Nicolaides, AG. Panayiotou, NC. Onland-Moret, YT. van der Schouw, G. Matullo, G. Fiorito, S. Guarrera, C. Sacerdote, NJ. Wareham, C. Langenberg, R. Scott, J. Luan, M. Bobak, S. Malyutina, A. Pająk, R. Kubinova, A. Tamosiunas, H. Pikhart, LL. Husemoen, N. Grarup, O. Pedersen, T. Hansen, A. Linneberg, KS. Simonsen, J. Cooper, SE. Humphries, M. Brilliant, T. Kitchner, H. Hakonarson, DS. Carrell, CA. McCarty, HL. Kirchner, EB. Larson, DR. Crosslin, M. de Andrade, DM. Roden, JC. Denny, C. Carty, S. Hancock, J. Attia, E. Holliday, M. O'Donnell, S. Yusuf, M. Chong, G. Pare, P. van der Harst, MA. Said, RN. Eppinga, N. Verweij, H. Snieder, . , T. Christen, DO. Mook-Kanamori, S. Gustafsson, L. Lind, E. Ingelsson, R. Pazoki, O. Franco, A. Hofman, A. Uitterlinden, A. Dehghan, A. Teumer, S. Baumeister, M. Dörr, MM. Lerch, U. Völker, H. Völzke, J. Ward, JP. Pell, DJ. Smith, T. Meade, AH. Maitland-van der Zee, EV. Baranova, R. Young, I. Ford, A. Campbell, S. Padmanabhan, ML. Bots, DE. Grobbee, P. Froguel, D. Thuillier, B. Balkau, A. Bonnefond, B. Cariou, M. Smart, Y. Bao, M. Kumari, A. Mahajan, PM. Ridker, DI. Chasman, AP. Reiner, LA. Lange, MD. Ritchie, FW. Asselbergs, JP. Casas, BJ. Keating, D. Preiss, AD. Hingorani, . , N. Sattar,
- 520 9_
- $a BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. METHODS: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m2, -0·09 to 0·30). INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins. FUNDING: British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.
- 650 _2
- $a krevní glukóza $x metabolismus $7 D001786
- 650 _2
- $a studie případů a kontrol $7 D016022
- 650 _2
- $a LDL-cholesterol $x krev $x genetika $7 D008078
- 650 _2
- $a kohortové studie $7 D015331
- 650 _2
- $a diabetes mellitus 2. typu $x krev $x diagnóza $x genetika $7 D003924
- 650 _2
- $a genetická predispozice k nemoci $x genetika $7 D020022
- 650 _2
- $a genetická variace $x genetika $7 D014644
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a mendelovská randomizace $x metody $7 D057182
- 650 _2
- $a proproteinkonvertasa subtilisin/kexin typu 9 $x genetika $7 D000071449
- 650 _2
- $a randomizované kontrolované studie jako téma $x metody $7 D016032
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Swerdlow, Daniel I $u Institute of Cardiovascular Science, University College London, UK; Department of Medicine, Imperial College London, London, UK.
- 700 1_
- $a Holmes, Michael V $u Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK; Medical Research Council Population Health Research Unit at the University of Oxford, University of Oxford, Oxford, UK.
- 700 1_
- $a Patel, Riyaz S $u Institute of Cardiovascular Science, University College London, UK; Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, UK; The Barts Heart Centre, St Bartholomew's Hospital, London, UK.
- 700 1_
- $a Fairhurst-Hunter, Zammy $u Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
- 700 1_
- $a Lyall, Donald M $u Institute of Health & Wellbeing, University of Glasgow, Glasgow, UK.
- 700 1_
- $a Hartwig, Fernando Pires $u Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
- 700 1_
- $a Horta, Bernardo Lessa $u Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
- 700 1_
- $a Hyppönen, Elina $u Centre for Population Health Research, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia; Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, UK; South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
- 700 1_
- $a Power, Christine $u Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, UK.
- 700 1_
- $a Moldovan, Max $u School of Health Sciences, University of South Australia, Adelaide, SA, Australia; South Australian Health and Medical Research Institute-EMBL Australia, Adelaide, SA, Australia.
- 700 1_
- $a van Iperen, Erik $u Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, Netherlands; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center Amsterdam, Netherlands.
- 700 1_
- $a Hovingh, G Kees $u Department of Vascular Medicine, Academic Medical Center Amsterdam, Netherlands.
- 700 1_
- $a Demuth, Ilja $u Charité Research Group on Geriatrics, Charité-Universitätsmedizin Berlin, Berlin, Germany; Institute of Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
- 700 1_
- $a Norman, Kristina $u Charité Research Group on Geriatrics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
- 700 1_
- $a Steinhagen-Thiessen, Elisabeth $u Charité Research Group on Geriatrics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
- 700 1_
- $a Demuth, Juri $u E.CA Economics GmbH, Berlin, Germany.
- 700 1_
- $a Bertram, Lars $u Neuroepidemiology and Ageing Research Unit, Imperial College London, London, UK; Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institutes of Neurogenetics and Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.
- 700 1_
- $a Liu, Tian $u Max Planck Institute for Human Development, Berlin, Germany; Max Planck Institute for Molecular Genetics, Berlin, Germany.
- 700 1_
- $a Coassin, Stefan $u Division of Genetic Epidemiology Innsbruck, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
- 700 1_
- $a Willeit, Johann $u Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
- 700 1_
- $a Kiechl, Stefan $u Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
- 700 1_
- $a Willeit, Karin $u Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
- 700 1_
- $a Mason, Dan $u Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, UK.
- 700 1_
- $a Wright, John $u Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, UK.
- 700 1_
- $a Morris, Richard $u School of Social and Community Medicine, University of Bristol, Bristol, UK.
- 700 1_
- $a Wanamethee, Goya $u Department of Primary Care & Population Health, University College London, UK.
- 700 1_
- $a Whincup, Peter $u Population Health Research Institute, St George's, University of London, London, UK.
- 700 1_
- $a Ben-Shlomo, Yoav $u School of Social and Community Medicine, University of Bristol, Bristol, UK.
- 700 1_
- $a McLachlan, Stela $u Centre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
- 700 1_
- $a Price, Jackie F $u Centre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
- 700 1_
- $a Kivimaki, Mika $u Department of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, UK.
- 700 1_
- $a Welch, Catherine $u Department of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, UK.
- 700 1_
- $a Sanchez-Galvez, Adelaida $u Department of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, UK.
- 700 1_
- $a Marques-Vidal, Pedro $u Internal Medicine Unit, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
- 700 1_
- $a Nicolaides, Andrew $u Department of Vascular Surgery, Imperial College London, London, UK; Department of Surgery, Nicosia Medical School, University of Nicosia, Nicosia, Cyprus.
- 700 1_
- $a Panayiotou, Andrie G $u Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Limassol, Cyprus.
- 700 1_
- $a Onland-Moret, N Charlotte $u Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
- 700 1_
- $a van der Schouw, Yvonne T $u Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
- 700 1_
- $a Matullo, Giuseppe $u Human Genetics Foundation, HuGeF, Turin, Italy; Department of Medical Sciences, University of Turin, Turin, Italy.
- 700 1_
- $a Fiorito, Giovanni $u Human Genetics Foundation, HuGeF, Turin, Italy; Department of Medical Sciences, University of Turin, Turin, Italy.
- 700 1_
- $a Guarrera, Simonetta $u Human Genetics Foundation, HuGeF, Turin, Italy; Department of Medical Sciences, University of Turin, Turin, Italy.
- 700 1_
- $a Sacerdote, Carlotta $u Cancer Epidemiology Unit, San Giovanni Battista Hospital, Turin, Italy; Centre for Oncology Prevention, CPO Piemonte, Turin, Italy.
- 700 1_
- $a Wareham, Nicholas J $u MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
- 700 1_
- $a Langenberg, Claudia $u MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
- 700 1_
- $a Scott, Robert $u MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
- 700 1_
- $a Luan, Jian'an $u MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
- 700 1_
- $a Bobak, Martin $u Department of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, UK.
- 700 1_
- $a Malyutina, Sofia $u Novosibirsk State Medical University, Novosibirsk, Russia; Institute of Internal and Preventive Medicine, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Russia.
- 700 1_
- $a Pająk, Andrzej $u Jagiellonian University Collegium Medicum, Krakow, Poland.
- 700 1_
- $a Kubinova, Ruzena $u National Institute of Public Health, Prague, Czech Republic.
- 700 1_
- $a Tamosiunas, Abdonas $u Lithuanian University of Health Sciences, Kaunas, Lithuania.
- 700 1_
- $a Pikhart, Hynek $u Department of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, UK.
- 700 1_
- $a Husemoen, Lise Lotte Nystrup $u Research Centre for Prevention and Health, Capital Region of Denmark, Denmark.
- 700 1_
- $a Grarup, Niels $u Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- 700 1_
- $a Pedersen, Oluf $u Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- 700 1_
- $a Hansen, Torben $u Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- 700 1_
- $a Linneberg, Allan $u Research Centre for Prevention and Health, Capital Region of Denmark, Denmark; Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- 700 1_
- $a Simonsen, Kenneth Starup $u Research Centre for Prevention and Health, Capital Region of Denmark, Denmark.
- 700 1_
- $a Cooper, Jackie $u Centre for Cardiovascular Genetics, University College London, UK.
- 700 1_
- $a Humphries, Steve E $u Centre for Cardiovascular Genetics, University College London, UK.
- 700 1_
- $a Brilliant, Murray $u Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA.
- 700 1_
- $a Kitchner, Terrie $u Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA.
- 700 1_
- $a Hakonarson, Hakon $u Children's Hospital of Philadelphia, Philadelphia, PA, USA.
- 700 1_
- $a Carrell, David S $u Group Health Research Institute in Seattle, WA, USA.
- 700 1_
- $a McCarty, Catherine A $u Essentia Institute of Rural Health, Duluth, MN, USA.
- 700 1_
- $a Kirchner, H Lester $u Center for Health Research, Geisinger Clinic, Danville, PA, USA.
- 700 1_
- $a Larson, Eric B $u Group Health Research Institute, Seattle, WA, USA.
- 700 1_
- $a Crosslin, David R $u Group Health Research Institute, Seattle, WA, USA.
- 700 1_
- $a de Andrade, Mariza $u Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
- 700 1_
- $a Roden, Dan M $u Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
- 700 1_
- $a Denny, Joshua C $u Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, USA.
- 700 1_
- $a Carty, Cara $u George Washington University, Washington, DC, USA.
- 700 1_
- $a Hancock, Stephen $u University of Newcastle, Newcastle, NSW, Australia.
- 700 1_
- $a Attia, John $u University of Newcastle, Newcastle, NSW, Australia.
- 700 1_
- $a Holliday, Elizabeth $u University of Newcastle, Newcastle, NSW, Australia.
- 700 1_
- $a O'Donnell, Martin $u Population Health Research Institute, Hamilton, ON, Canada.
- 700 1_
- $a Yusuf, Salim $u Population Health Research Institute, Hamilton, ON, Canada.
- 700 1_
- $a Chong, Michael $u Population Health Research Institute, Hamilton, ON, Canada.
- 700 1_
- $a Pare, Guillaume $u Population Health Research Institute, Hamilton, ON, Canada.
- 700 1_
- $a van der Harst, Pim $u Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, Netherlands; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
- 700 1_
- $a Said, M Abdullah $u Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
- 700 1_
- $a Eppinga, Ruben N $u Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
- 700 1_
- $a Verweij, Niek $u Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
- 700 1_
- $a Snieder, Harold $u Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
- 700 1_
- $a ,
- 700 1_
- $a Christen, Tim $u Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
- 700 1_
- $a Mook-Kanamori, Dennis O $u Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
- 700 1_
- $a Gustafsson, Stefan $u Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
- 700 1_
- $a Lind, Lars $u Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
- 700 1_
- $a Ingelsson, Erik $u Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
- 700 1_
- $a Pazoki, Raha $u Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
- 700 1_
- $a Franco, Oscar $u Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
- 700 1_
- $a Hofman, Albert $u Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
- 700 1_
- $a Uitterlinden, Andre $u Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.
- 700 1_
- $a Dehghan, Abbas $u Faculty of Medicine, and Department of Biostatistics and Epidemiology, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
- 700 1_
- $a Teumer, Alexander $u Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), Greifswald, Germany.
- 700 1_
- $a Baumeister, Sebastian $u Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.
- 700 1_
- $a Dörr, Marcus $u Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), Greifswald, Germany.
- 700 1_
- $a Lerch, Markus M $u Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
- 700 1_
- $a Völker, Uwe $u Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), Greifswald, Germany.
- 700 1_
- $a Völzke, Henry $u Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), Greifswald, Germany.
- 700 1_
- $a Ward, Joey $u Institute of Health & Wellbeing, University of Glasgow, Glasgow, UK.
- 700 1_
- $a Pell, Jill P $u Institute of Health & Wellbeing, University of Glasgow, Glasgow, UK.
- 700 1_
- $a Smith, Daniel J $u Institute of Health & Wellbeing, University of Glasgow, Glasgow, UK.
- 700 1_
- $a Meade, Tom $u Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
- 700 1_
- $a Maitland-van der Zee, Anke H $u Department of Respiratory Medicine, Academic Medical Center Amsterdam, Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.
- 700 1_
- $a Baranova, Ekaterina V $u Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.
- 700 1_
- $a Young, Robin $u Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
- 700 1_
- $a Ford, Ian $u Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
- 700 1_
- $a Campbell, Archie $u Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
- 700 1_
- $a Padmanabhan, Sandosh $u Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
- 700 1_
- $a Bots, Michiel L $u Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
- 700 1_
- $a Grobbee, Diederick E $u Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
- 700 1_
- $a Froguel, Philippe $u Department of Genomics of Common Disease, Imperial College London, London, UK; CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France.
- 700 1_
- $a Thuillier, Dorothée $u CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France.
- 700 1_
- $a Balkau, Beverley $u Renal and Cardiovascular Epidemiology, Centre de Recherche en Epidémiologie et Santé des Populations (CESP), INSERM U1018, Villejuif, France.
- 700 1_
- $a Bonnefond, Amélie $u Department of Genomics of Common Disease, Imperial College London, London, UK; CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France.
- 700 1_
- $a Cariou, Bertrand $u I'institut du Thorax, INSERM, CNRS, University of Nantes, CHU de Nantes, Nantes, France.
- 700 1_
- $a Smart, Melissa $u Institute for Social and Economic Research, University of Essex, Colchester, Essex, UK.
- 700 1_
- $a Bao, Yanchun $u Institute for Social and Economic Research, University of Essex, Colchester, Essex, UK.
- 700 1_
- $a Kumari, Meena $u Institute for Social and Economic Research, University of Essex, Colchester, Essex, UK.
- 700 1_
- $a Mahajan, Anubha $u Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
- 700 1_
- $a Ridker, Paul M $u Harvard Medical School Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA, USA.
- 700 1_
- $a Chasman, Daniel I $u Harvard Medical School Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA, USA.
- 700 1_
- $a Reiner, Alex P $u Department of Epidemiology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.
- 700 1_
- $a Lange, Leslie A $u Anschutz Medical Campus, University of Colorado Denver, Denver, CO, USA.
- 700 1_
- $a Ritchie, Marylyn D $u Biomedical and Translational Informatics, Geisinger Health System, Danville, PA, USA; Department of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA.
- 700 1_
- $a Asselbergs, Folkert W $u Institute of Cardiovascular Science, University College London, UK; Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, UK; Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, Netherlands.
- 700 1_
- $a Casas, Juan-Pablo $u Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, UK.
- 700 1_
- $a Keating, Brendan J $u Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
- 700 1_
- $a Preiss, David $u Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK; Medical Research Council Population Health Research Unit at the University of Oxford, University of Oxford, Oxford, UK.
- 700 1_
- $a Hingorani, Aroon D $u Institute of Cardiovascular Science, University College London, UK; Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, UK.
- 700 1_
- $a ,
- 700 1_
- $a Sattar, Naveed $u Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. Electronic address: naveed.sattar@glasgow.ac.uk.
- 773 0_
- $w MED00186388 $t The lancet. Diabetes & endocrinology $x 2213-8595 $g Roč. 5, č. 2 (2017), s. 97-105
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/27908689 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20180709 $b ABA008
- 991 __
- $a 20180718113023 $b ABA008
- 999 __
- $a ok $b bmc $g 1317372 $s 1022162
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2017 $b 5 $c 2 $d 97-105 $e 20161129 $i 2213-8595 $m The lancet. Diabetes & endocrinology $n Lancet Diabetes Endocrinol $x MED00186388
- LZP __
- $a Pubmed-20180709
