Mendelian randomization of blood lipids for coronary heart disease.

Autor:	Holmes MV; Genetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK Division of Transplant Surgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104, USA mvholmes@gmail.com., Asselbergs FW; 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., Palmer TM; Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK., Drenos F; Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, Rayne Building, London WC1E 6JF, UK MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK., Lanktree MB; Department of Medicine, McMaster University, Hamilton, ON, Canada L8S 4L8., Nelson CP; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK., Dale CE; Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK., Padmanabhan S; Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK., Finan C; Genetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK., Swerdlow DI; Genetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK., Tragante V; Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands Department of Medical Genetics, Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands., van Iperen EP; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands., Sivapalaratnam S; Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105 AZ, The Netherlands., Shah S; Department of Genetics Environment and Evolution, UCL Genetics Institute, 2nd Floor, Darwin Building, Gower Street, London WC1E 6BT, UK., Elbers CC; Department of Medical Genetics, Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Shah T; Genetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK., Engmann J; Genetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK., Giambartolomei C; Department of Genetics Environment and Evolution, UCL Genetics Institute, 2nd Floor, Darwin Building, Gower Street, London WC1E 6BT, UK., White J; Department of Genetics Environment and Evolution, UCL Genetics Institute, 2nd Floor, Darwin Building, Gower Street, London WC1E 6BT, UK., Zabaneh D; Department of Genetics Environment and Evolution, UCL Genetics Institute, 2nd Floor, Darwin Building, Gower Street, London WC1E 6BT, UK., Sofat R; Genetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK., McLachlan S; Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK., Doevendans PA; Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands., Balmforth AJ; Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK., Hall AS; Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK., North KE; Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA., Almoguera B; Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Hoogeveen RC; Baylor College of Medicine, Department of Medicine, Division of Atherosclerosis and Vascular Medicine, Houston, TX 77030, USA., Cushman M; Department of Medicine, University of Vermont, 208 South Park Dr, Colchester, VT 05446, USA Department of Pathology, University of Vermont, 208 South Park Dr, Colchester, VT 05446, USA., Fornage M; The University of Texas Health Science Center at Houston, Houston, TX, USA., Patel SR; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Redline S; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Siscovick DS; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA Department of Epidemiology, University of Washington, Seattle, WA, USA., Tsai MY; Department of Laboratory Medicine and Pathology, University of Minnesota., Karczewski KJ; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA., Hofker MH; Department Pathology and Medical Biology, Medical Biology Division, Molecular Genetics, University Medical Center Groningen and Groningen University, Groningen, The Netherlands., Verschuren WM; Centre for Prevention and Health Services Research at National Institute for Public Health and the Environment, Utrecht, The Netherlands., Bots ML; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., van der Schouw YT; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., Melander O; Lund University, Malmö, Sweden., Dominiczak AF; Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK., Morris R; Department of Primary Care and Population Health, UCL, Royal Free Campus, Rowland Hill St, London, UK., Ben-Shlomo Y; School of Social and Community Medicine, University of Bristol., Price J; Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK., Kumari M; Genetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK., Baumert J; Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Peters A; Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Thorand B; Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Koenig W; Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany., Gaunt TR; MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK., Humphries SE; Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, Rayne Building, London WC1E 6JF, UK., Clarke R; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., Watkins H; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK., Farrall M; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK., Wilson JG; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA., Rich SS; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA., de Bakker PI; Department of Medical Genetics, Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., Lange LA; Department of Genetics, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill,NC27514, USA., Davey Smith G; MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK., Reiner AP; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA., Talmud PJ; Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, Rayne Building, London WC1E 6JF, UK., Kivimäki M; Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 6BT, UK., Lawlor DA; MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK., Dudbridge F; Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK., Samani NJ; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK., Keating BJ; Division of Transplant Surgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104, USA Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA Department of Paediatrics, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Hingorani AD; Genetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK., Casas JP; Genetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Jazyk:	angličtina
Zdroj:	European heart journal [Eur Heart J] 2015 Mar 01; Vol. 36 (9), pp. 539-50. Date of Electronic Publication: 2014 Jan 27.
DOI:	10.1093/eurheartj/eht571
Abstrakt:	Aims: To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. Methods and Results: We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a prior meta-analysis (threshold P < 2 × 10(-6)); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P ≤ 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestricted allele score (48 SNPs) was associated with CHD (OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). Conclusion: The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain. (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu