Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts (Articolo in rivista)

Type
Label
  • Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Alternative label
  • Karani S. Vimaleswaran equal contributor,Diane J. Berry equal contributor,Chen Lu,Emmi Tikkanen, Stefan Pilz,Linda T. Hiraki, Jason D. Cooper, Zari Dastani, Rui Li, Denise K. Houston, Andrew R. Wood, Karl Michaëlsson, Liesbeth Vandenput Lina Zgaga, Laura M. Yerges-Armstrong, Mark I. McCarthy, Josée Dupuis,Marika Kaakinen,Marcus E. Kleber,Karen Jameson,Nigel Arden, Olli Raitakari,Jorma Viikari, Kurt K. Lohman,Luigi Ferrucci,Håkan Melhus, Erik Ingelsson, Liisa Byberg,Lars Lind, Mattias Lorentzon,Veikko Salomaa, Harry Campbell, Malcolm Dunlop, Braxton D. Mitchell,Karl-Heinz Herzig, Anneli Pouta, Anna-Liisa Hartikainen,the Genetic Investigation of Anthropometric Traits (GIANT) consortium, Elizabeth A. Streeten, Evropi Theodoratou, Antti Jula, Nicholas J. Wareham,Claes Ohlsson, Timothy M. Frayling, Stephen B. Kritchevsky, Timothy D. Spector, J. Brent Richards,Terho Lehtimäki,Willem H. Ouwehand,Peter Kraft, Cyrus Cooper, Winfried März, Chris Power, Ruth J. F. Loos, Thomas J. Wang Marjo-Riitta Järvelin, John C. Whittaker,Aroon D. Hingorani, Elina Hyppönen. Collaborators (375). (2013)
    Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts
    in PLoS medicine (Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Karani S. Vimaleswaran equal contributor,Diane J. Berry equal contributor,Chen Lu,Emmi Tikkanen, Stefan Pilz,Linda T. Hiraki, Jason D. Cooper, Zari Dastani, Rui Li, Denise K. Houston, Andrew R. Wood, Karl Michaëlsson, Liesbeth Vandenput Lina Zgaga, Laura M. Yerges-Armstrong, Mark I. McCarthy, Josée Dupuis,Marika Kaakinen,Marcus E. Kleber,Karen Jameson,Nigel Arden, Olli Raitakari,Jorma Viikari, Kurt K. Lohman,Luigi Ferrucci,Håkan Melhus, Erik Ingelsson, Liisa Byberg,Lars Lind, Mattias Lorentzon,Veikko Salomaa, Harry Campbell, Malcolm Dunlop, Braxton D. Mitchell,Karl-Heinz Herzig, Anneli Pouta, Anna-Liisa Hartikainen,the Genetic Investigation of Anthropometric Traits (GIANT) consortium, Elizabeth A. Streeten, Evropi Theodoratou, Antti Jula, Nicholas J. Wareham,Claes Ohlsson, Timothy M. Frayling, Stephen B. Kritchevsky, Timothy D. Spector, J. Brent Richards,Terho Lehtimäki,Willem H. Ouwehand,Peter Kraft, Cyrus Cooper, Winfried März, Chris Power, Ruth J. F. Loos, Thomas J. Wang Marjo-Riitta Järvelin, John C. Whittaker,Aroon D. Hingorani, Elina Hyppönen. Collaborators (375). (literal)
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  • Gli autori dell'IRGB sono inclusi tra i collaboratori all'interno del the Genetic Investigation of Anthropometric Traits (GIANT) consortium. (literal)
Rivista
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  • 1Centre for Paediatric Epidemiology and Biostatistics and MRC Centre of Epidemiology for Child Health, UCL Institute of Child Health, London, United Kingdom, 2Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America, 3Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland, 4National Institute for Health and Welfare, Helsinki, Finland, 5Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Austria, 6Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands, 7Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, 8Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institut efor Medical Research, University of Cambridge, Cambridge, United Kingdom, 9Department of Epidemiology, Biostatistics and Occupational Health, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada, 10Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada, 11Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston Salem, North Carolina, United States of America, 12Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, United Kingdom, 13Department of Surgical Sciences, Uppsala University, Uppsala, Sweden, 14Center for Bone and Arthritis Research, Department of Internal Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden, 15Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom, 16Andrija Stampar School of Public Health, Medical School University of Zagreb, Zagreb, Croatia, 17University of Maryland School of Medicine, Division of Endocrinology, Baltimore, Maryland, United States of America, 18Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, United Kingdom, 19Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, 20Oxford NIHR Biomedical ResearchCentre, Churchill Hospital, Headington, Oxford, United Kingdom, 21National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, United States of America, 22Institute of Health Sciences and Biocenter Oulu, University of Oulu, Oulu, Finland, 23LURIC Study non-profit LLC, Freiburg, Germany and Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany, 24MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom, 25NIHR Musculoskeletal BRU, Botnar Research Centre, Oxford, United Kingdom, 26MRCLifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom, 27Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland, 28Department ofMedicine, University of Turku and Turku University Hospital, Turku, Finland, 29Department of Biostatistical Sciences, Division of Public Health Sciences, Wake ForestSchool of Medicine, Winston Salem, North Carolina, United States of America, 30Clinical Research Branch, Harbor Hospital, Baltimore, Maryland, United States of America, 31Department of Medical Sciences, Uppsala University, Uppsala, Sweden, 32Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm,Sweden, 33Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom, 34MRCHuman Genetics Unit Western General Hospital Edinburgh, United Kingdom, 35Institute of Biomedicine, University of Oulu, Oulu, Finland, 36Department of Psychiatry,Kuopio University Hospital, Kuopio, Finland, 37Department of Public Health Science and General Practice, University of Oulu, Oulu, Finland, 38Department of Obstetricsand Gynaecology and Public Health and General Practice, University of Oulu, Oulu, Finland, 39MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke'sHospital, Cambridge, United Kingdom, 40Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom, 41Department ofClinical Chemistry, Fimlab Laboratories, Tampere University Hospital and University of Tampere, Tampere, Finland, 42Department of Haematology, University ofCambridge, United Kingdom, 43Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom, 44NHS Blood and Transplant, Cambridge, United Kingdom, 45Synlab Academy, Mannheim, Germany, 46Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany, 47Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, United States of America, 48Department of Biostatistics andEpidemiology, School of Public Health, MRC-HPA Centre for Environment and Health, Imperial College, Faculty of Medicine, London, United Kingdom, 49Department ofChildren, Young People and Families, National Institute for Health and Welfare, Oulu, Finland, 50Department of Epidemiology and Population Health, London School ofHygiene and Tropical Medicine, London, United Kingdom, 51Quantitative Sciences, GlaxoSmithKline, Stevenage, United Kingdom, 52Genetic Epidemiology Group,Department of Epidemiology and Public Health, Division of Population Health, University College London, London, United Kingdom, 53Division of Medicine, Centre forClinical Pharmacology, University College London, London, United Kingdom (literal)
Titolo
  • Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts (literal)
Abstract
  • BACKGROUND: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. METHODS AND FINDINGS: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10?²?). The BMI allele score was associated both with BMI (p = 6.30×10??²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p<=8.07×10??? for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p>=0.57 for both vitamin D scores). CONCLUSIONS: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency. (literal)
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