Financiado en parte por Amgen, Eli Lilly and Company, GlaxoSmithKline, Novo Nordisk Fonden, Servier
Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts
Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Hiraki LT, Cooper JD, Dastani Z, Li R, Houston DK, Wood AR, Michaëlsson K, Vandenput L, Zgaga L, Yerges-Armstrong LM, McCarthy MI, Dupuis J, Kaakinen M, Kleber ME, Jameson K, Arden N, Raitakari O, Viikari J, Lohman KK, Ferrucci L, Melhus H, Ingelsson E, Byberg L, Lind L, Lorentzon M, Salomaa V, Campbell H, Dunlop M, Mitchell BD, Herzig KH, Pouta A, Hartikainen AL, Genetic Investigation of Anthropometric Traits-GIANT Consortium, Streeten EA, Theodoratou E, Jula A, Wareham NJ, Ohlsson C, Frayling TM, Kritchevsky SB, Spector TD, Richards JB, Lehtimäki T, Ouwehand WH, Kraft P, Cooper C, März W, Power C, Loos RJ, Wang TJ, Järvelin MR, Whittaker JC, Hingorani AD, Hyppönen E
PLoS medicine · 706 citas
Etiquetas de revisión
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Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiado por la industria
- Empresa
- Amgen
- Empresa
- Eli Lilly and Company
- Empresa
- GlaxoSmithKline
- Universidad u hospital
- London School of Hygiene and Tropical Medicine
- Organización sin fines de lucro
- Wellcome Trust
- Organización sin fines de lucro
- Cancer Research UK
- Gobierno
- National Institute for Health and Care Research
- Organización sin fines de lucro
- British Heart Foundation
- Universidad u hospital
- University College London
- Universidad u hospital
- Great Ormond Street Hospital for Children
- Empresa
- Novo Nordisk Fonden
- Empresa
- Servier
- Organización sin fines de lucro
- Versus Arthritis
- Gobierno
- Canadian Institutes of Health Research
- Gobierno
- Medical Research Council
- Gobierno
- National Institute on Alcohol Abuse and Alcoholism
- Gobierno
- National Institute on Aging
- Gobierno
- National Institute for Health Research (NIHR)
- Gobierno
- NIA NIH HHS
- Gobierno
- Chief Scientist Office
- Gobierno
- NIAAA NIH HHS
- Autores
- Al menos un autor declara un vínculo económico con la industria
- Subvenciones
- National Institute on Aging (P30 AG021332); National Institute on Aging (K01 AG030506); National Institute on Alcohol Abuse and Alcoholism (K05AA017688); Medical Research Council (G0601653); Versus Arthritis (17413); Versus Arthritis (13181); Novo Nordisk Fonden (NNF13OC0005785); Versus Arthritis (13157); British Heart Foundation (FS05/125); National Institute for Health and Care Research (NF-SI-0611-10136); Novo Nordisk Fonden (#NNF10OC1013354); Versus Arthritis (13147); National Institute for Health and Care Research (NF-SI-0508-10082); British Heart Foundation (PG/09/023/26806); Versus Arthritis (16349); National Institute for Health and Care Research (NF-SI-0611-10099); Cancer Research UK (14136); National Institute for Health and Care Research (NF-SI-0512-10114); Versus Arthritis (17265); National Institute for Health and Care Research (NF-SI-0611-10219); British Heart Foundation (PG/09/023); Medical Research Council (MC_UU_12011/1); Medical Research Council (MC_UU_12015/1); Wellcome Trust (090532); Novo Nordisk Fonden (NNF11OC1014660); Versus Arthritis (16095); Cancer Research UK (12076); Versus Arthritis (13230); Versus Arthritis (13085); Wellcome Trust (096964/Z/11/Z)
Según 21 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2013-02-05 · PLoS Med · vol. 10 · número 2 · pág. e1001383
- Editorial
- Public Library of Science
- Citado
- 1,045 citas · más que el 100% de estudios similares · 71.0× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 54 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY
- Áreas de investigación
- Vitamin D Research Studies · Genetic Associations and Epidemiology · Nutrition, Genetics, and Disease
- Palabras clave
- obesity, vitamin D deficiency, 25-hydroxyvitamin D, body mass index, bidirectional causality, genetic instruments, vitamin D status, confounding adjustment
- MeSH
- humans, vitamin d deficiency, obesity, genetic predisposition to disease, vitamin d, body mass index, multivariate analysis, linear models, risk assessment, risk factors, evidence-based medicine, phenotype, polymorphism, single nucleotide, adult, aged, aged, 80 and over, middle aged, north america, europe, female, male, mendelian randomization analysis, biomarkers, white people
58 autores
- Karani Santhanakrishnan Vimaleswaran🇬🇧University College London
- Diane J. Berry🇬🇧University College London
- Chen Lu🇺🇸Boston University
- Emmi Tikkanen🇫🇮University of Helsinki; Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland
- Stefan Pilz🇦🇹🇳🇱Medical University of Graz; Amsterdam Public Health; Amsterdam UMC Location Vrije Universiteit Amsterdam
- Linda T. Hiraki🇺🇸Harvard University
- Jason D. Cooper🇬🇧University of Cambridge; Wellcome Trust
- Zari Dastani🇨🇦Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Rui Li🇨🇦Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Denise K. Houston🇺🇸Wake Forest University Health Sciences; Wake Forest University
- Andrew R. Wood🇬🇧University of Exeter; Peninsula College of Medicine and Dentistry
- Karl Michaëlsson🇸🇪Uppsala University
- Liesbeth Vandenput🇸🇪University of Gothenburg
- Lina Zgaga🇭🇷🇬🇧University of Zagreb; Andrija Stampar Teaching Institute of Public Health; University of Edinburgh
- Laura M. Yerges-Armstrong🇺🇸University of Maryland, Baltimore
- Mark I. McCarthy🇬🇧Centre for Human Genetics; Churchill Hospital; University of Oxford; NIHR Oxford Biomedical Research Centre; Oxford Centre for Diabetes, Endocrinology and Metabolism
- Josée Dupuis🇺🇸Boston University; Framingham Heart Study
- Marika Kaakinen🇫🇮University of Oulu
- Marcus Edi Kleber🇩🇪Heidelberg University; Medizinische Fakultät Mannheim
- Karen Jameson🇬🇧MRC Lifecourse Epidemiology Unit; University of Southampton
- Nigel Arden🇬🇧MRC Lifecourse Epidemiology Unit; University of Southampton
- Olli Tuomas Raitakari🇫🇮University of Turku; Turku University Hospital
- Jorma Viikari🇫🇮University of Turku; Turku University Hospital
- Kurt K. Lohman🇺🇸Wake Forest University
- Luigi Ferrucci🇺🇸MedStar Harbor Hospital
- Håkan Melhus🇸🇪Uppsala University
- Erik Ingelsson🇸🇪Karolinska Institutet
- Liisa Byberg🇸🇪Uppsala University
- Lars Lind🇸🇪Uppsala University
- Mattias Lorentzon🇸🇪University of Gothenburg
- Veikko V Salomaa🇫🇮Finnish Institute for Health and Welfare
- Harry Campbell🇬🇧University of Edinburgh
- Malcolm G. Dunlop🇬🇧Western General Hospital; Institute of Genetics and Cancer; MRC Human Genetics Unit; University of Edinburgh
- Braxton D. Mitchell🇺🇸University of Maryland, Baltimore
- Karl‐Heinz Herzig🇫🇮Kuopio University Hospital; University of Oulu
- Anneli Pouta🇫🇮University of Oulu
- Anna‐Liisa Hartikainen🇫🇮University of Oulu
- Elizabeth A. Streeten🇺🇸University of Maryland, Baltimore
- Evropi Τheodoratou🇬🇧University of Edinburgh
- Antti Jula🇫🇮Finnish Institute for Health and Welfare
- Nicholas J. Wareham🇬🇧Addenbrooke's Hospital; MRC Epidemiology Unit
- Claes Ohlsson🇸🇪University of Gothenburg
- Timothy M. Frayling🇬🇧University of Exeter; Peninsula College of Medicine and Dentistry
- Stephen B. Kritchevsky🇺🇸Wake Forest University Health Sciences; Wake Forest University
- Tim D. Spector🇬🇧King's College London
- John Brent Richards🇬🇧🇨🇦King's College London; Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Terho J. Lehtimäki🇫🇮Tampere University Hospital; Fimlab (Finland); University of Tampere
- Willem Hendrik Ouwehand🇬🇧NHS Blood and Transplant; University of Cambridge; Wellcome Sanger Institute
- Peter Kraft🇺🇸Harvard University
- Cyrus C. Cooper🇬🇧MRC Lifecourse Epidemiology Unit; University of Southampton
- Winfried März🇩🇪Heidelberg University; Synlab (Germany); Medizinische Fakultät Mannheim
- Chris Power🇬🇧University College London
- Ruth J. F. Loos🇬🇧Addenbrooke's Hospital; MRC Epidemiology Unit
- Thomas J. Wang🇺🇸Massachusetts General Hospital
- Marjo‐Riitta Järvelin🇫🇮🇬🇧Finnish Institute for Health and Welfare; Imperial College London; University of Oulu
- John C. Whittaker🇬🇧GlaxoSmithKline (United Kingdom); London School of Hygiene & Tropical Medicine
- Aroon Dinesh Hingorani🇬🇧University College London
- Elina Hyppönen🇬🇧 · autor de correspondenciaUniversity College London
Resumen
El texto original del estudio, en el idioma en que se publicó.
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 = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) 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≤8.07×10⁻⁵⁷ 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.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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