OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

Atherosclerosis Research Unit Center for Molecular Medicine Department of Medicine Karolinska Institutet Stockholm Sweden

Atherosclerosis Research Unit Center for Molecular Medicine Department of Medicine Karolinska Institutet Stockholm Sweden Center for Molecular Medicine Karolinska University Hospital Solna Stockholm Sweden

Baylor College of Medicine Department of Medicine Division of Atherosclerosis and Vascular Medicine Houston Texas 77030 USA

Beth Israel Deaconess Medical Center Boston Massachusetts USA

British Heart Foundation Glasgow Cardiovascular Research Centre University of Glasgow Glasgow UK

Cardiovascular Health Research Unit Departments of Medicine Epidemiology and Health Services University of Washington Seattle WA USA Group Health Research Institute Group Health Cooperative Seattle WA USA

Center for Applied Genomics Abramson Research Center The Children's Hospital of Philadelphia Philadelphia USA

Center for Applied Genomics Abramson Research Center The Children's Hospital of Philadelphia Philadelphia USA BGI Shenzhen Beishan Industrial Zone Yantian District Shenzhen 518083 China

Center for Experimental Medicine Institute for Clinical and Experimental Medicine Videnska 1958 9 Prague 4 14021 Czech Republic

Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care University of Cambridge Cambridge UK

Centre for Cardiovascular Genetics Institute of Cardiovascular Science University College London London UK

Centre for Cardiovascular Genetics Institute of Cardiovascular Science University College London London UK WC1E 6JF

Centre for Health Monitoring National Institute of Public Health 100 42 Prague Czech Republic

Centre for Paediatric Epidemiology and Biostatistics UCL Institute of Child Health London UK

Centre for Paediatric Epidemiology and Biostatistics UCL Institute of Child Health London UK School of Population Health and Sansom Institute for Health Research University of South Australia Adelaide SA 5000 Australia South Australian Health and Medical Research Institute Adelaide SA5000 Australia

Centre for Population Health Sciences University of Edinburgh Edinburgh EH8 9AG UK

College of Pharmacy The University of New Mexico Albuquerque NM USA

Cyprus International Institute for Environmental and Public Health in association with the Harvard School of Public Health Cyprus University of Technology 3603 Limassol Cyprus

Danish Cancer Society Strandboulevarden Copenhagen Denmark

Department of Biostatistics Boston University School of Public Health Boston Massachusetts USA National Heart Lung and Blood Institute's The Framingham Heart Study Framingham Massachusetts USA

Department of Cardiology Division Heart and Lungs University Medical Center Utrecht Utrecht The Netherlands

Department of Cardiology Division Heart and Lungs University Medical Center Utrecht Utrecht The Netherlands Durrer Center for Cardiogenetic Research ICIN Netherlands Heart Institute Utrecht The Netherlands Institute of Cardiovascular Science Faculty of Population Health Sciences University College London London UK

Department of Cardiology Leiden University Medical Center the Netherlands

Department of Cardiology University Medical Center Groningen Groningen The Netherlands

Department of Cardiology University Medical Center Groningen Groningen The Netherlands Department of Genetics University Medical Center Groningen Groningen The Netherlands Durrer Center for Cardiogenetic Research ICIN Netherlands Heart Institute Utrecht The Netherlands

Department of Clinical Biochemistry Royal Perth Hospital and School of Surgery the University of Western Australia

Department of Clinical Sciences Lund University Malmö Sweden

Department of Epidemiology and Department of Nutrition Harvard School of Public Health Boston MA USA Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA USA

Department of Epidemiology and Population Studies Institute of Public Health Jagiellonian University Medical College 31 531 Krakow Poland

Department of Epidemiology and Public Health University College London London WC1E 6BT UK

Department of Epidemiology Erasmus Medical Center Rotterdam The Netherlands

Department of Epidemiology Harvard School of Public Health Boston MA USA

Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Johns Hopkins University Baltimore Maryland USA

Department of Genetics University of North Carolina School of Medicine at Chapel Hill Chapel Hill North Carolina 27514 USA

Department of Internal Medicine Internal Medicine CHUV Lausanne Switzerland

Department of Laboratory Medicine and Pathology University of Minnesota USA

Department of Medical Sciences Uppsala University Uppsala University Hospital SE 751 85 Uppsala Sweden

Department of Medicine McMaster University Hamilton Ontario Canada L8S4L8

Department of Neurology Sir Charles Gairdner Hospital Perth Australia School of Medicine and Pharmacology The University of Western Australia Nedlands Perth Australia

Department of Neuroscience Mayo Clinic Florida Jacksonville FL USA

Department of Physiology and Biophysics University of Mississippi Medical Center Jackson MS USA

Department of Population Studies Institute of Cardiology Lithuanian University of Health Sciences Kaunas LT 50161 Lithuania

Department of Preventive Cardiology Institute for Clinical and Experimental Medicine Prague 4 14021 Czech Republic

Department of Primary Care and Population Health UCL London UK

Department of Primary Care and Public Health and Primary Care University of Cambridge Cambridge UK

Department of Public Health and Caring Sciences Uppsala University Uppsala University Hospital SE 75185 Uppsala Sweden

Department of Radiology University Medical Center Utrecht Utrecht The Netherlands

Department of Surgery Penn Transplant Institute Perelman School of Medicine University of Pennsylvania Philadelphia PA19104 USA Center for Applied Genomics Abramson Research Center The Children's Hospital of Philadelphia Philadelphia USA

Department of Vascular Medicine University Medical Center Utrecht Utrecht The Netherlands

Dept Pathology and Medical Biology Medical Biology division Molecular Genetics University Medical Center Groningen and Groningen University Groningen The Netherlands

Division of Epidemiology School of Public Health University of Texas Health Science Center at Houston Texas USA

Division of Health Sciences Warwick Medical School University of Warwick Coventry UK

Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands

Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle WA 98109 USA

Division of Research Kaiser Permanente Northern California Oakland CA USA

Division of Sleep and Circadian Disorders Brigham and Women's Hospital

Faculty of Epidemiology and Population Health London School of Hygiene and Tropical Medicine London WC1E 7HT UK

Faculty of Epidemiology and Population Health London School of Hygiene and Tropical Medicine London WC1E 7HT UK Centre for Statistical Methodology London School of Hygiene and Tropical Medicine London WC1E 7HT UK

Faculty of Epidemiology and Population Health London School of Hygiene and Tropical Medicine London WC1E 7HT UK Genetics R and D GlaxoSmithKline Stevenage UK

Genetic Epidemiology Group Institute of Cardiovascular Science Department of Epidemiology and Public Health University College London UK

Genetic Epidemiology Group Institute of Cardiovascular Science Department of Epidemiology and Public Health University College London UK Department of Surgery Penn Transplant Institute Perelman School of Medicine University of Pennsylvania Philadelphia PA19104 USA Center for Clinical Epidemiology and Biostatistics Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA

Genetic Epidemiology Group Institute of Cardiovascular Science Department of Epidemiology and Public Health University College London UK Faculty of Epidemiology and Population Health London School of Hygiene and Tropical Medicine London WC1E 7HT UK

German Institute of Human Nutrition Potsdam Rehbrücke Arthur Scheunert Allee 114 116 14558 Nuthetal Germany

Harvard Medical School Boston USA

Harvard Medical School Boston USA Beth Israel Deaconess Medical Center Boston Massachusetts USA

Institute for Translational Genomics and Population Sciences Los Angeles BioMedical Research Institute and Department of Pediatrics Harbor UCLA Medical Center Torrance Calif USA

Institute of Cardiovascular and Medical Sciences College of Medical Veterinary and Life Sciences University of Glasgow Glasgow G12 8TA UK

Institute of Internal and Preventative Medicine Siberian Branch of Russian Academy of Medical Sciences Novosibirsk Russia 630089 Dept of Internal Medicine Novosibirsk State Medical University Novosibirsk Russia 630091

Institute of Internal and Preventative Medicine Siberian Branch of Russian Academy of Medical Sciences Novosibirsk Russia 630089 Faculty of Medicine Novosibirsk State University Novosibirsk Russia 630090

Institute of Molecular Medicine University of Texas Health Science Center at Houston Texas USA

Instituto Medicina Molecular Faculdade de Medicina Universidade de Lisboa 1649 028 Lisbon Portugal Servico Neurologia Hospital de Santa Maria 1649 035 Lisbon Portugal

Instituto Nacional de Saude Doutor Ricardo Jorge 1649 016 Lisbon Portugal Faculdade Ciencias Universidade Lisboa 1749 016 Lisbon Portugal

Instituto Nacional de Saude Doutor Ricardo Jorge 1649 016 Lisbon Portugal Instituto Gulbenkian Ciencia P 2780 156 Oeiras Portugal Biofig Center for Biodiversity Functional and Integrative Genomics Campus da FCUL 1749 016 Lisboa Portugal

Julius Center for Health Sciences and Primary Care University Medical Center Utrecht The Netherlands

Julius Center for Health Sciences and Primary Care University Medical Center Utrecht The Netherlands Department of Medical Genetics Center for Molecular Medicine University Medical Center Utrecht Utrecht The Netherlands

Mayo Clinic Department of Neurology Jacksonville FL 32224 USA

MRC Epidemiology Unit Institute of Metabolic Science Addenbrooke's Hospital Cambridge UK

MRC Integrative Epidemiology Unit at the Universty of Bristol Oakfield House Bristol BS8 2BN UK

MRC Unit for Lifelong Health and Ageing at UCL London UK

National Heart Lung and Blood Institute's The Framingham Heart Study Framingham Massachusetts USA

National Institute for Public Health and the Environment Bilthoven the Netherlands

National Institute of Public Health University of Southern Denmark Copenhagen Denmark

New York Academy of Medicine New York NY 10021 USA

Northwestern University Feinberg School of Medicine Department of Preventive Medicine Chicago IL USA

Office of Public Health Genomics Office of Epidemiology Surveillance and Laboratory Services Centers for Disease Control and Prevention Atlanta GA 30333 USA

Population Health Research Institute St George's University of London London UK

Preventive Medicine and Epidemiology Evans Department of Medicine Boston University School of Medicine Boston Massachusetts USA

Research Centre for Prevention and Health Capital Region of Denmark Glostrup University Hospital Glostrup Denmark

Robertson Centre for Biostatistics University of Glasgow Glasgow UK

School of Health Sciences Jackson State University Jackson MS USA

School of Public Health University of Minnesota Minneapolis Minnesota USA

School of Surgery University of Western Australia Perth Australia

The Copenhagen General Population Study Herlev Hospital Copenhagen Denmark Faculty of Health Sciences Copenhagen University Hospital University of Copenhagen Copenhagen Denmark Department of Clinical Biochemistry Herlev Hospital Copenhagen University Hospital Denmark

UCL Genetics Institute Department of Genetics Environment and Evolution London WC1E 6BT UK

UCL Institute of Health Equity Department of Epidemiology and Public Health London WC1E 7HB UK

Unit of Cancer Epidemiology San Giovanni Battista Hospital and Center for Cancer Prevention 10129 Torino Italy

Vascular Screening and Diagnostic Centre Ayios Dometios Nicosia Cyprus Deparment of Vascular Surgery Imperial College London SW7 2BX UK Cyprus Cardiovascular Disease Educational and Research trust Nicosia Cyprus

Vavilov Institute of General Genetics Russian Academy of Sciences Moscow Russia

Wellcome Trust Centre for Human Genetics University of Oxford Oxford UK Department of Cardiovascular Medicine University of Oxford Oxford UK

Western Australian Centre for Health and Ageing Centre for Medical Research University of Western Australia Perth Australia

Western Australian Centre for Health and Ageing Centre for Medical Research University of Western Australia Perth Australia School of Psychiatry and Clinical Neurosciences University of Western Australia Perth 6009 Australia Department of Psychiatry Royal Perth Hospital Perth Australia

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$a Holmes, Michael V $u Genetic Epidemiology Group, Institute of Cardiovascular Science, Department of Epidemiology and Public Health, University College London, UK Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA19104, USA Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

245    10

$a Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data / $c MV. Holmes, CE. Dale, L. Zuccolo, RJ. Silverwood, Y. Guo, Z. Ye, D. Prieto-Merino, A. Dehghan, S. Trompet, A. Wong, A. Cavadino, D. Drogan, S. Padmanabhan, S. Li, A. Yesupriya, M. Leusink, J. Sundstrom, JA. Hubacek, H. Pikhart, DI. Swerdlow, AG. Panayiotou, SA. Borinskaya, C. Finan, S. Shah, KB. Kuchenbaecker, T. Shah, J. Engmann, L. Folkersen, P. Eriksson, F. Ricceri, O. Melander, C. Sacerdote, DM. Gamble, S. Rayaprolu, OA. Ross, S. McLachlan, O. Vikhireva, I. Sluijs, RA. Scott, V. Adamkova, L. Flicker, FM. Bockxmeer, C. Power, P. Marques-Vidal, T. Meade, MG. Marmot, JM. Ferro, S. Paulos-Pinheiro, SE. Humphries, PJ. Talmud, I. Mateo Leach, N. Verweij, A. Linneberg, T. Skaaby, PA. Doevendans, MJ. Cramer, P. van der Harst, OH. Klungel, NF. Dowling, AF. Dominiczak, M. Kumari, AN. Nicolaides, C. Weikert, H. Boeing, S. Ebrahim, TR. Gaunt, JF. Price, L. Lannfelt, A. Peasey, R. Kubinova, A. Pajak, S. Malyutina, MI. Voevoda, A. Tamosiunas, AH. Maitland-van der Zee, PE. Norman, GJ. Hankey, MM. Bergmann, A. Hofman, OH. Franco, J. Cooper, J. Palmen, W. Spiering, PA. de Jong, D. Kuh, R. Hardy, AG. Uitterlinden, MA. Ikram, I. Ford, E. Hyppönen, OP. Almeida, NJ. Wareham, KT. Khaw, A. Hamsten, LL. Husemoen, A. Tjønneland, JS. Tolstrup, E. Rimm, JW. Beulens, WM. Verschuren, NC. Onland-Moret, MH. Hofker, SG. Wannamethee, PH. Whincup, R. Morris, AM. Vicente, H. Watkins, M. Farrall, JW. Jukema, J. Meschia, LA. Cupples, SJ. Sharp, M. Fornage, C. Kooperberg, AZ. LaCroix, JY. Dai, MB. Lanktree, DS. Siscovick, E. Jorgenson, B. Spring, J. Coresh, YR. Li, SG. Buxbaum, PJ. Schreiner, RC. Ellison, MY. Tsai, SR. Patel, S. Redline, AD. Johnson, RC. Hoogeveen, H. Hakonarson, JI. Rotter, E. Boerwinkle, PI. de Bakker, M. Kivimaki, FW. Asselbergs, N. Sattar, DA. Lawlor, J. Whittaker, G. Davey Smith, K. Mukamal, BM. Psaty, JG. Wilson, LA. Lange, A. Hamidovic, AD. Hingorani, BG. Nordestgaard, M. Bobak, DA. Leon, C. Langenberg, TM. Palmer, AP. Reiner, BJ. Keating, F. Dudbridge, JP. Casas, . ,

520    9_

$a OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

650    _2

$a dospělí $7 D000328

650    _2

$a senioři $7 D000368

650    _2

$a alkoholdehydrogenasa $x genetika $7 D000426

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$a koronární nemoc $x krev $x etiologie $x genetika $7 D003327

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$a časopisecké články $7 D016428

655    _2

$a metaanalýza $7 D017418

655    _2

$a Research Support, N.I.H., Extramural $7 D052061

655    _2

$a práce podpořená grantem $7 D013485

655    _2

$a Research Support, U.S. Gov't, P.H.S. $7 D013487

700    1_

$a Dale, Caroline E $u Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.

700    1_

$a Zuccolo, Luisa $u MRC Integrative Epidemiology Unit (IEU) at the Universty of Bristol, Oakfield House, Bristol BS8 2BN, UK.

700    1_

$a Silverwood, Richard J $u Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK Centre for Statistical Methodology, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.

700    1_

$a Guo, Yiran $u Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, USA BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.

700    1_

$a Ye, Zheng $u MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

700    1_

$a Prieto-Merino, David $u Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.

700    1_

$a Dehghan, Abbas $u Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

700    1_

$a Trompet, Stella $u Department of Cardiology, Leiden University Medical Center, the Netherlands.

700    1_

$a Wong, Andrew $u MRC Unit for Lifelong Health and Ageing at UCL, London, UK.

700    1_

$a Cavadino, Alana $u Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK.

700    1_

$a Drogan, Dagmar $u German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.

700    1_

$a Padmanabhan, Sandosh $u Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.

700    1_

$a Li, Shanshan $u Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Juan-P.Casas@lshtm.ac.uk.

700    1_

$a Yesupriya, Ajay $u Office of Public Health Genomics, Office of Epidemiology, Surveillance, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

700    1_

$a Leusink, Maarten $u Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

700    1_

$a Sundstrom, Johan $u Department of Medical Sciences, Uppsala University, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.

700    1_

$a Hubacek, Jaroslav A $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Videnska 1958/9, Prague 4, 14021, Czech Republic.

700    1_

$a Pikhart, Hynek $u Department of Epidemiology and Public Health, University College London, London, WC1E 6BT, UK.

700    1_

$a Swerdlow, Daniel I $u Genetic Epidemiology Group, Institute of Cardiovascular Science, Department of Epidemiology and Public Health, University College London, UK.

700    1_

$a Panayiotou, Andrie G $u Cyprus International Institute for Environmental and Public Health in association with the Harvard School of Public Health, Cyprus University of Technology, 3603 Limassol, Cyprus.

700    1_

$a Borinskaya, Svetlana A $u Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.

700    1_

$a Finan, Chris $u Genetic Epidemiology Group, Institute of Cardiovascular Science, Department of Epidemiology and Public Health, University College London, UK.

700    1_

$a Shah, Sonia $u UCL Genetics Institute, Department of Genetics Environment and Evolution, London, WC1E 6BT, UK.

700    1_

$a Kuchenbaecker, Karoline B $u Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

700    1_

$a Shah, Tina $u Genetic Epidemiology Group, Institute of Cardiovascular Science, Department of Epidemiology and Public Health, University College London, UK.

700    1_

$a Engmann, Jorgen $u Genetic Epidemiology Group, Institute of Cardiovascular Science, Department of Epidemiology and Public Health, University College London, UK.

700    1_

$a Folkersen, Lasse $u Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

700    1_

$a Eriksson, Per $u Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

700    1_

$a Ricceri, Fulvio $u Unit of Cancer Epidemiology, San Giovanni Battista Hospital and Center for Cancer Prevention (CPO-Piemonte), 10129, Torino, Italy.

700    1_

$a Melander, Olle $u Department of Clinical Sciences, Lund University, Malmö, Sweden.

700    1_

$a Sacerdote, Carlotta $u Unit of Cancer Epidemiology, San Giovanni Battista Hospital and Center for Cancer Prevention (CPO-Piemonte), 10129, Torino, Italy.

700    1_

$a Gamble, Dale M $u Mayo Clinic Department of Neurology, Jacksonville, FL 32224, USA.

700    1_

$a Rayaprolu, Sruti $u Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.

700    1_

$a Ross, Owen A $u Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.

700    1_

$a McLachlan, Stela $u Centre for Population Health Sciences, University of Edinburgh, Edinburgh EH8 9AG, UK.

700    1_

$a Vikhireva, Olga $u Department of Epidemiology and Public Health, University College London, London, WC1E 6BT, UK.

700    1_

$a Sluijs, Ivonne $u Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.

700    1_

$a Scott, Robert A $u MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

700    1_

$a Adamkova, Vera $u Department of Preventive Cardiology, Institute for Clinical and Experimental Medicine, Prague 4, 14021, Czech Republic. $7 gn_A_00001463

700    1_

$a Flicker, Leon $u Western Australian Centre for Health & Ageing, Centre for Medical Research, University of Western Australia, Perth, Australia.

700    1_

$a Bockxmeer, Frank M van $u Department of Clinical Biochemistry, Royal Perth Hospital and School of Surgery, the University of Western Australia.

700    1_

$a Power, Christine $u Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK.

700    1_

$a Marques-Vidal, Pedro $u Department of Internal Medicine, Internal Medicine, CHUV, Lausanne, Switzerland.

700    1_

$a Meade, Tom $u Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.

700    1_

$a Marmot, Michael G $u UCL Institute of Health Equity, Department of Epidemiology & Public Health, London WC1E 7HB, UK.

700    1_

$a Ferro, Jose M $u Instituto Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, 1649-028 Lisbon, Portugal Servico Neurologia, Hospital de Santa Maria, 1649-035 Lisbon, Portugal.

700    1_

$a Paulos-Pinheiro, Sofia $u Instituto Nacional de Saude Doutor Ricardo Jorge, 1649-016 Lisbon, Portugal Faculdade Ciencias Universidade Lisboa, 1749-016 Lisbon, Portugal.

700    1_

$a Humphries, Steve E $u Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.

700    1_

$a Talmud, Philippa J $u Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.

700    1_

$a Mateo Leach, Irene $u Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.

700    1_

$a Verweij, Niek $u Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.

700    1_

$a Linneberg, Allan $u Research Centre for Prevention and Health, Capital Region of Denmark, Glostrup University Hospital, Glostrup, Denmark.

700    1_

$a Skaaby, Tea $u Research Centre for Prevention and Health, Capital Region of Denmark, Glostrup University Hospital, Glostrup, Denmark.

700    1_

$a Doevendans, Pieter A $u Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.

700    1_

$a Cramer, Maarten J $u Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.

700    1_

$a van der Harst, Pim $u Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.

700    1_

$a Klungel, Olaf H $u Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

700    1_

$a Dowling, Nicole F $u Office of Public Health Genomics, Office of Epidemiology, Surveillance, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

700    1_

$a Dominiczak, Anna F $u Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.

700    1_

$a Kumari, Meena $u Genetic Epidemiology Group, Institute of Cardiovascular Science, Department of Epidemiology and Public Health, University College London, UK.

700    1_

$a Nicolaides, Andrew N $u Vascular Screening and Diagnostic Centre, Ayios Dometios, Nicosia, Cyprus Deparment of Vascular Surgery, Imperial College, London, SW7 2BX, UK Cyprus Cardiovascular Disease Educational and Research trust, Nicosia, Cyprus.

700    1_

$a Weikert, Cornelia $u German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.

700    1_

$a Boeing, Heiner $u German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.

700    1_

$a Ebrahim, Shah $u Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.

700    1_

$a Gaunt, Tom R $u MRC Integrative Epidemiology Unit (IEU) at the Universty of Bristol, Oakfield House, Bristol BS8 2BN, UK.

700    1_

$a Price, Jackie F $u Centre for Population Health Sciences, University of Edinburgh, Edinburgh EH8 9AG, UK.

700    1_

$a Lannfelt, Lars $u Department of Public Health & Caring Sciences, Uppsala University, Uppsala University Hospital, SE-75185 Uppsala, Sweden.

700    1_

$a Peasey, Anne $u Department of Epidemiology and Public Health, University College London, London, WC1E 6BT, UK.

700    1_

$a Kubinova, Ruzena $u Centre for Health Monitoring, National Institute of Public Health, 100 42 Prague, Czech Republic.

700    1_

$a Pajak, Andrzej $u Department of Epidemiology and Population Studies, Institute of Public Health, Jagiellonian University Medical College, 31-531 Krakow, Poland.

700    1_

$a Malyutina, Sofia $u Institute of Internal and Preventative Medicine, Siberian Branch of Russian Academy of Medical Sciences, Novosibirsk, Russia, 630089 Dept of Internal Medicine, Novosibirsk State Medical University, Novosibirsk, Russia, 630091.

700    1_

$a Voevoda, Mikhail I $u Institute of Internal and Preventative Medicine, Siberian Branch of Russian Academy of Medical Sciences, Novosibirsk, Russia, 630089 Faculty of Medicine, Novosibirsk State University, Novosibirsk, Russia, 630090.

700    1_

$a Tamosiunas, Abdonas $u Department of Population Studies, Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania.

700    1_

$a Maitland-van der Zee, Anke H $u Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

700    1_

$a Norman, Paul E $u School of Surgery, University of Western Australia, Perth, Australia.

700    1_

$a Hankey, Graeme J $u Department of Neurology, Sir Charles Gairdner Hospital, Perth, Australia School of Medicine and Pharmacology, The University of Western Australia, Nedlands, Perth, Australia.

700    1_

$a Bergmann, Manuela M $u German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.

700    1_

$a Hofman, Albert $u Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

700    1_

$a Franco, Oscar H $u Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

700    1_

$a Cooper, Jackie $u Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK WC1E 6JF.

700    1_

$a Palmen, Jutta $u Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.

700    1_

$a Spiering, Wilko $u Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.

700    1_

$a de Jong, Pim A $u Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.

700    1_

$a Kuh, Diana $u MRC Unit for Lifelong Health and Ageing at UCL, London, UK.

700    1_

$a Hardy, Rebecca $u MRC Unit for Lifelong Health and Ageing at UCL, London, UK.

700    1_

$a Uitterlinden, Andre G $u Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

700    1_

$a Ikram, M Arfan $u Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

700    1_

$a Ford, Ian $u Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.

700    1_

$a Hyppönen, Elina $u Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK School of Population Health and Sansom Institute for Health Research, University of South Australia, Adelaide SA 5000, Australia South Australian Health and Medical Research Institute, Adelaide SA5000, Australia.

700    1_

$a Almeida, Osvaldo P $u Western Australian Centre for Health & Ageing, Centre for Medical Research, University of Western Australia, Perth, Australia School of Psychiatry & Clinical Neurosciences (M573), University of Western Australia, Perth 6009, Australia Department of Psychiatry, Royal Perth Hospital, Perth, Australia.

700    1_

$a Wareham, Nicholas J $u MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

700    1_

$a Khaw, Kay-Tee $u Department of Primary Care and Public Health and Primary Care, University of Cambridge, Cambridge, UK.

700    1_

$a Hamsten, Anders $u Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.

700    1_

$a Husemoen, Lise Lotte N $u Research Centre for Prevention and Health, Capital Region of Denmark, Glostrup University Hospital, Glostrup, Denmark.

700    1_

$a Tjønneland, Anne $u Danish Cancer Society, Strandboulevarden, Copenhagen, Denmark.

700    1_

$a Tolstrup, Janne S $u National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.

700    1_

$a Rimm, Eric $u Department of Epidemiology and Department of Nutrition, Harvard School of Public Health, Boston, MA, USA Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

700    1_

$a Beulens, Joline W J $u Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.

700    1_

$a Verschuren, W M Monique $u National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

700    1_

$a Onland-Moret, N Charlotte $u Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.

700    1_

$a Hofker, Marten H $u Dept Pathology and Medical Biology, Medical Biology division, Molecular Genetics, University Medical Center Groningen and Groningen University, Groningen, The Netherlands.

700    1_

$a Wannamethee, S Goya $u Department of Primary Care & Population Health, UCL, London, UK.

700    1_

$a Whincup, Peter H $u Population Health Research Institute, St George's, University of London, London, UK.

700    1_

$a Morris, Richard $u Department of Primary Care & Population Health, UCL, London, UK.

700    1_

$a Vicente, Astrid M $u Instituto Nacional de Saude Doutor Ricardo Jorge, 1649-016 Lisbon, Portugal Instituto Gulbenkian Ciencia, P-2780-156 Oeiras, Portugal Biofig - Center for Biodiversity, Functional and Integrative Genomics, Campus da FCUL, 1749-016 Lisboa, Portugal.

700    1_

$a Watkins, Hugh $u Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK Department of Cardiovascular Medicine, University of Oxford, Oxford, UK.

700    1_

$a Farrall, Martin $u Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK Department of Cardiovascular Medicine, University of Oxford, Oxford, UK.

700    1_

$a Jukema, J Wouter $u Department of Cardiology, Leiden University Medical Center, the Netherlands.

700    1_

$a Meschia, James $u Mayo Clinic Department of Neurology, Jacksonville, FL 32224, USA.

700    1_

$a Cupples, L Adrienne $u Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, Massachusetts, USA.

700    1_

$a Sharp, Stephen J $u MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

700    1_

$a Fornage, Myriam $u Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Texas, USA.

700    1_

$a Kooperberg, Charles $u Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

700    1_

$a LaCroix, Andrea Z $u Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

700    1_

$a Dai, James Y $u Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

700    1_

$a Lanktree, Matthew B $u Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8S4L8.

700    1_

$a Siscovick, David S $u New York Academy of Medicine, New York, NY 10021, USA.

700    1_

$a Jorgenson, Eric $u Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

700    1_

$a Spring, Bonnie $u Northwestern University, Feinberg School of Medicine, Department of Preventive Medicine, Chicago, IL, USA.

700    1_

$a Coresh, Josef $u Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.

700    1_

$a Li, Yun R $u Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, USA Juan-P.Casas@lshtm.ac.uk.

700    1_

$a Buxbaum, Sarah G $u School of Health Sciences, Jackson State University, Jackson, MS, USA.

700    1_

$a Schreiner, Pamela J $u School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.

700    1_

$a Ellison, R Curtis $u Preventive Medicine and Epidemiology, Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.

700    1_

$a Tsai, Michael Y $u Department of Laboratory Medicine and Pathology, University of Minnesota, USA.

700    1_

$a Patel, Sanjay R $u Division of Sleep and Circadian Disorders, Brigham and Women's Hospital; Harvard Medical School, Boston USA Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

700    1_

$a Redline, Susan $u Division of Sleep and Circadian Disorders, Brigham and Women's Hospital; Harvard Medical School, Boston USA.

700    1_

$a Johnson, Andrew D $u National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, Massachusetts, USA.

700    1_

$a Hoogeveen, Ron C $u Baylor College of Medicine, Department of Medicine, Division of Atherosclerosis & Vascular Medicine, Houston, Texas 77030, USA.

700    1_

$a Hakonarson, Hakon $u Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, USA.

700    1_

$a Rotter, Jerome I $u Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, Calif, USA.

700    1_

$a Boerwinkle, Eric $u Division of Epidemiology, School of Public Health, University of Texas Health Science Center at Houston, Texas, USA.

700    1_

$a de Bakker, Paul I W $u Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.

700    1_

$a Kivimaki, Mika $u Department of Epidemiology and Public Health, University College London, London, WC1E 6BT, UK.

700    1_

$a Asselbergs, Folkert W $u Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK.

700    1_

$a Sattar, Naveed $u British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.

700    1_

$a Lawlor, Debbie A $u MRC Integrative Epidemiology Unit (IEU) at the Universty of Bristol, Oakfield House, Bristol BS8 2BN, UK.

700    1_

$a Whittaker, John $u Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK Genetics, R&D, GlaxoSmithKline, Stevenage, UK.

700    1_

$a Davey Smith, George $u MRC Integrative Epidemiology Unit (IEU) at the Universty of Bristol, Oakfield House, Bristol BS8 2BN, UK.

700    1_

$a Mukamal, Kenneth $u Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

700    1_

$a Psaty, Bruce M $u Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA,USA Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.

700    1_

$a Wilson, James G $u Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.

700    1_

$a Lange, Leslie A $u Department of Genetics, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, North Carolina 27514, USA.

700    1_

$a Hamidovic, Ajna $u College of Pharmacy, The University of New Mexico, Albuquerque, NM, USA.

700    1_

$a Hingorani, Aroon D $u Genetic Epidemiology Group, Institute of Cardiovascular Science, Department of Epidemiology and Public Health, University College London, UK.

700    1_

$a Nordestgaard, Børge G $u The Copenhagen General Population Study, Herlev Hospital, Copenhagen, Denmark Faculty of Health Sciences, Copenhagen University Hospital, University of Copenhagen,Copenhagen, Denmark Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Denmark.

700    1_

$a Bobak, Martin $u Department of Epidemiology and Public Health, University College London, London, WC1E 6BT, UK.

700    1_

$a Leon, David A $u Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.

700    1_

$a Langenberg, Claudia $u MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

700    1_

$a Palmer, Tom M $u Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK.

700    1_

$a Reiner, Alex P $u Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

700    1_

$a Keating, Brendan J $u Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA19104, USA Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, USA.

700    1_

$a Dudbridge, Frank $u Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.

700    1_

$a Casas, Juan P $u Genetic Epidemiology Group, Institute of Cardiovascular Science, Department of Epidemiology and Public Health, University College London, UK Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK Juan-P.Casas@lshtm.ac.uk.

700    1_

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