Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/83628
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Type: Journal article
Title: Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts
Author: Vimaleswaran, K.
Palmer, L.
Citation: PLoS Medicine, 2013; 10(2):1001383-1-1001383-1 3
Publisher: Public Library of Science
Issue Date: 2013
ISSN: 1549-1277
1549-1676
Contributor: Palmer, Lyle John
Statement of
Responsibility: 
Karani S. Vimaleswaran ... the Genetic Investigation of Anthropometric Traits (GIANT) consortium ... et al.
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/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.
Keywords: Genetic Investigation of Anthropometric Traits-GIANT Consortium; 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; European Continental Ancestry Group; North America; Europe; Female; Male; Mendelian Randomization Analysis; Biomarkers
Description: Consortium members: Lyle J Palmer for the University of Adelaide.
Rights: © 2013 Vimaleswaran et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0020137903
DOI: 10.1371/journal.pmed.1001383
Appears in Collections:Medicine publications

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