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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Causal Relationship between Obesity and Vitamin D Status: Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts
PLoS Medicine, Volume 10, No. 2, Article e1001383, Year 2013
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Description
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/m2 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. Please see later in the article for the Editors' Summary. © 2013 Vimaleswaran et al.
Authors & Co-Authors
Vimaleswaran, Karani Santhanakrishnan
United Kingdom, London
Medical Research Council
Berry, Diane J.
United Kingdom, London
Medical Research Council
Tikkanen, Emmi
Finland, Helsinki
Helsingin Yliopisto
Finland, Helsinki
Terveyden ja Hyvinvoinnin Laitos
Hiraki, Linda T.
United States, Boston
Harvard T.h. Chan School of Public Health
Cooper, Jason D.
United Kingdom, Cambridge
University of Cambridge
Dastani, Zari
Canada, Montreal
Université Mcgill
Li, Rui
Canada, Montreal
Université Mcgill
Houston, Denise K.
United States, Winston Salem
Wake Forest University School of Medicine
Wood, Andrew R.
United Kingdom, Plymouth
Plymouth University, Peninsula Schools of Medicine and Dentistry
Michaëlsson, Karl
Sweden, Uppsala
Uppsala Universitet
Vandenput, Liesbeth
Sweden, Gothenburg
Göteborgs Universitet
Zgaga, Lina
United Kingdom, Edinburgh
The University of Edinburgh
Croatia, Zagreb
University of Zagreb School of Medicine
Yerges-Armstrong, Laura M.
United States, Baltimore
University of Maryland School of Medicine
McCarthy, Mark I.
United Kingdom, Oxford
Churchill Hospital
United Kingdom, Oxford
University of Oxford
United Kingdom, Oxford
Nihr Oxford Biomedical Research Centre
Dupuis, Josèe
United States, Boston
School of Public Health
United States, Framingham
Framingham Heart Study
Kaakinen, Marika A.
Finland, Oulu
Oulun Yliopisto
Kleber, Marcus Edi
Germany, Heidelberg
Universität Heidelberg
Jameson, Karen A.
United Kingdom, Southampton
University of Southampton
Arden, Nigel K.
United Kingdom, Southampton
University of Southampton
United Kingdom, Oxford
Nihr Oxford Biomedical Research Centre
Raitakari, Olli T.
Finland, Turku
Turun Yliopisto
Viikari, Jorma S.A.
Finland, Turku
Turun Yliopistollinen Keskussairaala
Lohman, Kurt K.
United States, Winston Salem
Wake Forest University School of Medicine
Ferrucci, Luigi G.
United States, Baltimore
Harbor Hospital
Ingelsson, Erik
Sweden, Stockholm
Karolinska Institutet
Lind, Lars L.
Sweden, Uppsala
Uppsala Universitet
Lorentzon, Mattias
Sweden, Gothenburg
Göteborgs Universitet
Salomaa, Veikko V.
Finland, Helsinki
Terveyden ja Hyvinvoinnin Laitos
Campbell, Harry
United Kingdom, Edinburgh
The University of Edinburgh
Dunlop, Malcolm G.
United Kingdom, Edinburgh
The University of Edinburgh
United Kingdom, Edinburgh
Mrc Human Genetics Unit
Herzig, Karl-Heinz
Finland, Oulu
Oulun Yliopisto
Finland, Kuopio
Kuopio University Hospital
Pouta, Anneli
Finland, Oulu
Oulun Yliopisto
Hartikainen -, Anna Liisa
Finland, Oulu
Oulun Yliopisto
Streeten, Elizabeth A.
United States, Baltimore
University of Maryland School of Medicine
Theodoratou, Evropi
United Kingdom, Edinburgh
The University of Edinburgh
Jula, Antti M.
Finland, Helsinki
Terveyden ja Hyvinvoinnin Laitos
Wareham, Nicholas J.
United Kingdom, Cambridge
Wellcome-mrc Institute of Metabolic Science
Ohlsson, Claes
Sweden, Gothenburg
Göteborgs Universitet
Frayling, Tim M.
United Kingdom, Plymouth
Plymouth University, Peninsula Schools of Medicine and Dentistry
Kritchevsky, Stephen B.
United States, Winston Salem
Wake Forest University School of Medicine
Spector, Tim David
United Kingdom, London
King's College London
Richards, John Brent
Canada, Montreal
Université Mcgill
United Kingdom, London
King's College London
Lehtimäki, Terho J.
Finland, Tampere
University Hospital of Tampere
Ouwehand, Willem Hendrik
United Kingdom, Cambridge
University of Cambridge
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, Bristol
Nhs Blood and Transplant
Kraft, Peter L.
United States, Boston
Harvard T.h. Chan School of Public Health
Cooper, Cyrus C.
United Kingdom, Southampton
University of Southampton
Mar̈z, Winfried
Germany, Munich
Synlab International Gmbh
Germany, Heidelberg
Universität Heidelberg
Power, Chris
United Kingdom, London
Medical Research Council
Loos, Ruth J.F.
United Kingdom, Cambridge
Wellcome-mrc Institute of Metabolic Science
J̈arvelin, Märjo Riitta R.
Finland, Oulu
Oulun Yliopisto
United Kingdom, London
Imperial College London
Finland, Helsinki
Terveyden ja Hyvinvoinnin Laitos
Whittaker, John C.
United Kingdom, London
London School of Hygiene & Tropical Medicine
United Kingdom, Brentford
Glaxosmithkline Plc.
Hingorani, Aroon Dinesh
United Kingdom, London
University College London
Hyppönen, Elina
United Kingdom, London
Medical Research Council
Speliotes, Elizabeth K.
Unknown Affiliation
Willer, Cristen J.
Unknown Affiliation
Berndt, Sonja I.
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Monda, Keri L.
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Thorleifsson, Gudmar
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Jackson, Anne U.
Unknown Affiliation
Allen, Hana Lango
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Lindgren, Cecilia M.
Unknown Affiliation
Luan, Jian'fan N.An
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Mägi, Reedik
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Randall, Joshua C.
Unknown Affiliation
Vedantam, Sailaja L.
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Winkler, Thomas W.
Unknown Affiliation
Qi, Llu
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Workalemahu, Tsegaselassie
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Heid, Iris Maria
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Steinthórsdóttir, Valgerdur
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Stringham, Heather M.
Unknown Affiliation
Weedon, Michael N.
Unknown Affiliation
Wheeler, Eleanor
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Ferreira, Teresa
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Segrè, Ayellet V.
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Nemesh, James C.
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Gustafsson, Stefan
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Kilpeläinen, Tuomas Oskari
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Bouatia-Naji, Nabila
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Esko, Tönu
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Feitosa, Mary Furlan
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Kutalik, Zoltán
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Mangino, Massimo
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Raychaudhuri, Soumya
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Scherag, André
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Smith, Albert Vernon
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Welch, Ryan P.
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Aben, Katja K.H.
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Lamina, Claudia
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Moffatt, Miriam F.
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Ripatti, Samuli O.
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van Duijn, Cornelia M.
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Barroso, Inês E.
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Statistics
Citations: 728
Authors: 338
Affiliations: 40
Identifiers
Doi:
10.1371/journal.pmed.1001383
ISSN:
15491277
Research Areas
Genetics And Genomics
Noncommunicable Diseases
Study Design
Randomised Control Trial
Cross Sectional Study
Cohort Study
Study Approach
Systematic review